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Results for “tumour microenvironment”

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PubMed2026

Multiregion profiling of genomic and transcriptional heterogeneity in head and neck squamous-cell carcinoma.

BACKGROUND: Intratumoral heterogeneity (ITH) is thought to contribute to tumour evolution and treatment resistance but its biological and clinical significance in localised head and neck squamous-cell carcinoma (HNSCC) remains incompletely understood. PATIENTS AND METHODS: In the prospective SCANDARE study, we analysed 87 patients with resectable HNSCC treated with upfront surgery. Two to five spatially distinct tumour regions per patient underwent pathological evaluation, targeted DNA sequencing, and bulk RNA sequencing. Genomic ITH (gITH) was quantified using clonal deconvolution and Shannon diversity indices, whereas transcriptional heterogeneity (tITH) was assessed using the intratumour expression distance metric. Associations between ITH, molecular features, tumour microenvironment composition, and clinical outcomes were explored using multivariable statistical models. RESULTS: Pathology-based spatial heterogeneity showed limited prognostic value. gITH was common, with 37% of tumours displaying regionally heterogeneous pathogenic variants, including spatially actionable alterations in 10% of patients. In an initial multivariable Cox model, higher gITH was associated with shorter disease-free survival. However, after Ridge-penalised modelling and bootstrap internal validation, the effect size was attenuated [corrected hazard ratio 1.42, 95% confidence interval (CI) 0.91-2.75]. The overall model retained moderate discriminative performance (optimism-corrected C-index 0.69, 95% CI 0.59-0.79). gITH was associated with tumour cellularity, reduced estimated endothelial cell infiltration, and alterations in KMT2C and PIK3CA. tITH differed according to human papillomavirus (HPV) status, with lower tITH in HPV-positive tumours, and was associated with distinct biological pathways and genomic alterations. Genomic and tITH were not correlated. CONCLUSIONS: This prospective multiregion study provides a comprehensive characterisation of genomic and tITH in localised HNSCC. Our findings highlight substantial spatial molecular diversity within primary tumours and suggest potential associations between heterogeneity, tumour biology, and clinical outcome that warrant validation in independent cohorts.

head and neck squamous-cell carcinoma (HNSCC)↗

PubMed2026

Myeloid landscape of BRAF-mutant papillary thyroid cancer and thyroiditis.

Papillary thyroid cancer (PTC) is less aggressive when associated with lymphocytic thyroiditis (LT), even in the presence of oncogenic BRAF, including smaller tumours, less lymph node involvement and reduced extrathyroidal extension. To investigate possible immune mechanisms underlying this association, we compared the tumour microenvironment of PTC-BRAF with LT and that without LT using single-cell RNA sequencing (scRNA-seq). Single-cell libraries were generated from fresh and fixed tumour samples with post-dissociation viability >70% using the 10x Genomics Chromium Platform and sequenced on an Illumina NovaSeq 6000. We analysed scRNA-seq data from 11 PTC-BRAF tumours: four with LT (one publicly available sample) and seven without LT. Downstream analyses included quality control, batch correction, dimensionality reduction, and differential gene expression analysis. We found that neutrophils were the predominant myeloid cell type in PTCs without LT. Thyrocytes without LT showed significant expression of the neutrophil recruitment chemokine ECRG4. In the absence of LT, neutrophils expressed oncogenic genes with poor clinical outcomes. In contrast, thyrocytes from tumours with LT showed increased expression of MHC-II antigen presentation, consistent with effective immune surveillance. Thyrocytes and macrophages in the presence of LT showed enrichment of interferon gamma response pathways. Our data suggest that LT in thyroid cancer is associated with enhanced antigen presentation and fewer features of pro-tumourigenic innate immune activity. These results identify previously under-recognised innate immune cell population and associated transcriptomic features, which suggest new mechanisms to target immune treatments in PTC refractory to other therapies.

Humans↗

PubMed2025

Cancer-induced nerve injury promotes resistance to anti-PD-1 therapy.

Perineural invasion (PNI) is a well-established factor of poor prognosis in multiple cancer types1, yet its mechanism remains unclear. Here we provide clinical and mechanistic insights into the role of PNI and cancer-induced nerve injury (CINI) in resistance to anti-PD-1 therapy. Our study demonstrates that PNI and CINI of tumour-associated nerves are associated with poor response to anti-PD-1 therapy among patients with cutaneous squamous cell carcinoma, melanoma and gastric cancer. Electron microscopy and electrical conduction analyses reveal that cancer cells degrade the nerve fibre myelin sheets. The injured neurons respond by autonomously initiating IL-6- and type I interferon-mediated inflammation to promote nerve healing and regeneration. As the tumour grows, the CINI burden increases, and its associated inflammation becomes chronic and skews the general immune tone within the tumour microenvironment into a suppressive and exhaustive state. The CINI-driven anti-PD-1 resistance can be reversed by targeting multiple steps in the CINI signalling process: denervating the tumour, conditional knockout of the transcription factor mediating the injury signal within neurons (Atf3), knockout of interferon-α receptor signalling (Ifnar1-/-) or by combining anti-PD-1 and anti-IL-6-receptor blockade. Our findings demonstrate the direct immunoregulatory roles of CINI and its therapeutic potential.

Animals↗

PubMed2017

Addressing current challenges in cancer immunotherapy with mathematical and computational modelling.

The goal of cancer immunotherapy is to boost a patient's immune response to a tumour. Yet, the design of an effective immunotherapy is complicated by various factors, including a potentially immunosuppressive tumour microenvironment, immune-modulating effects of conventional treatments and therapy-related toxicities. These complexities can be incorporated into mathematical and computational models of cancer immunotherapy that can then be used to aid in rational therapy design. In this review, we survey modelling approaches under the umbrella of the major challenges facing immunotherapy development, which encompass tumour classification, optimal treatment scheduling and combination therapy design. Although overlapping, each challenge has presented unique opportunities for modellers to make contributions using analytical and numerical analysis of model outcomes, as well as optimization algorithms. We discuss several examples of models that have grown in complexity as more biological information has become available, showcasing how model development is a dynamic process interlinked with the rapid advances in tumour-immune biology. We conclude the review with recommendations for modellers both with respect to methodology and biological direction that might help keep modellers at the forefront of cancer immunotherapy development.

Computer Simulation↗

PubMed2026

Malaria driven mechanisms shaping cancer risk and aggressiveness in African populations.

Malaria and cancer represent intersecting public health challenges in sub-Saharan Africa, where malaria remains endemic and cancer incidence is rapidly increasing. Emerging evidence indicates that chronic or recurrent malaria infection may influence carcinogenesis and tumour aggressiveness through complex biological mechanisms. This narrative review critically synthesizes data from PubMed, Scopus, and Web of Science to elucidate the mechanistic intersections between malaria and cancer risk, progression, and therapeutic response. The review highlights five principal axes linking malaria to oncogenesis: malaria-induced oxidative stress and chronic inflammation driving genomic instability; gut microbiome dysbiosis altering systemic immunity and tumour microenvironment; exploitation of shared molecular targets such as the endothelial protein C receptor (EPCR) and oncofetal chondroitin sulfate by Plasmodium parasites and cancer cells; cooperative interactions between malaria and oncogenic viruses like Epstein-Barr virus in lymphomagenesis; and malaria-associated vitamin D deficiency impairing immune surveillance. Furthermore, pharmacological evidence reveals that several antimalarial agents, including artemisinin derivatives, chloroquine, and quinacrine, possess anticancer properties, while some anticancer drugs exhibit antimalarial activity, underscoring opportunities for dual-action or repurposed therapeutics. The convergence of malaria and cancer biology underscores the urgent need for integrative, multidisciplinary research spanning molecular epidemiology, immunology, and pharmacology. Unveiling these mechanisms may unveil novel biomarkers and therapeutic targets, guiding context-specific interventions to reduce the disproportionate cancer burden in malaria-endemic African populations.

Humans↗

PubMed2026

Engineering controllable CAR T-cell therapies: from binary safety switches to programmable immunity.

Chimeric antigen receptor (CAR) T-cell therapy has revolutionised cancer gene therapy, yet its expansion into solid tumours is hindered by a critical vulnerability: the autonomous, "always-on" nature of conventional CAR constructs. This unregulated activity drives severe toxicities, including cytokine release syndrome (CRS) and on-target/off-tumour damage, while constitutive signalling in hostile tumour microenvironments (TMEs) accelerates T-cell exhaustion. Early safety strategies relied on irreversible genetic "kill switches," which sacrifice the therapeutic cell population entirely. This review traces the conceptual evolution of CAR T-cell controllability from binary elimination towards platforms enabling graded, reversible, and spatiotemporally precise regulation. We examine the transition from calibrated signalling architectures and small-molecule-regulated split-CARs to advanced optogenetic and sonogenetic controllers, detailing the biophysics of photoreceptor pairs and their preclinical efficacy. Furthermore, we explore complementary architectures, including autonomous logic-gated receptors. Finally, we propose that the optimal next-generation CAR T product will integrate calibrated signalling, external control, and context-dependent armouring to achieve truly programmable, safe, and durable cellular immunotherapy.

Humans↗

PubMed2026

Multiomics analysis reveals that senescent CXCL16+ macrophages promote lung adenocarcinoma progression through TGF-β signalling.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer and remains a leading cause of cancer-related mortality worldwide. Although, immunotherapy has become a cornerstone of first-line treatment, only 20-30% of patients achieve a durable clinical benefit, largely because of the complexity and heterogeneity of the tumour immune microenvironment. Emerging evidence indicates that cellular senescence, particularly within immune cells, contributes to tumour progression by impairing antitumour immunity; however, its mechanistic role in LUAD remains incompletely understood. METHODS: We performed an integrative multiomics analysis incorporating genome-wide association studies (GWASs), bulk RNA sequencing, single-cell RNA sequencing, and spatial transcriptomics to characterize immune heterogeneity in LUAD. Cellular senescence was validated by performing staining for senescence-associated β-galactosidase and the canonical markers p16 and p21. SHAP analysis was applied to evaluate the contribution of CXCL16+ macrophages. Functional roles were assessed using coculture assays, in vitro and in vivo tumour models, orthotopic tumour implantation, and multiplex immunofluorescence staining of clinical specimens. RESULTS: A summary data-based on Mendelian randomization analysis integrating GWAS and TCGA data identified CXCL16 as a senescence-associated gene that is causally linked to the LUAD risk. Single-cell RNA sequencing revealed that CXCL16 is predominantly expressed in macrophages, and the pseudotime analysis together with β-galactosidase staining confirmed its association with macrophage senescence. Spatial transcriptomics and immunofluorescence staining showed the marked enrichment of CXCL16+ macrophages in LUAD tissues. The cell-cell communication analysis further revealed a strong association between the number of CXCL16+ macrophages and the activation of the TGF-β signalling pathway within the tumour microenvironment. Functionally, CXCL16+ macrophages promoted LUAD progression via TGF-β signalling, as validated in vitro and in subcutaneous and orthotopic tumour models. Molecular dynamics simulations additionally suggested that LUAD patients with high levels of CXCL16+ macrophage infiltration may exhibit increased sensitivity to bosutinib. CONCLUSIONS: CXCL16 promotes macrophage senescence, and senescent CXCL16+ macrophages drive LUAD progression through TGF-β signalling. These findings identify CXCL16+ macrophages as a biologically and therapeutically relevant immune cell population, highlighting a potential target for precision intervention in LUAD.

Humans↗

PubMed2026

Long-Term Outcomes and Paired Immune and Genomic Exploratory Analyses After Neoadjuvant Dose-Dense MVAC in Muscle-Invasive Bladder Cancer: A Single-Centre Case Series.

Background/Objectives: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy has been the standard of care for muscle-invasive bladder cancer (MIBC) for two decades, yet a substantial proportion of patients derive no benefit. As antibody-drug conjugates and immune checkpoint inhibitors reshape perioperative treatment, it is unclear which patients retain meaningful benefit from platinum. We describe long-term outcomes and exploratory paired immune and genomic analyses in a single-centre cohort treated with dose-dense MVAC (dd-MVAC). Methods: We retrospectively identified 54 consecutive patients with MIBC treated with neoadjuvant dd-MVAC between November 2013 and November 2019. Forty-two underwent radical cystectomy and are assessable for pathologic response. Immunohistochemistry for CD3, CD8, FOXP3, PD-1, PD-L1, PD-L2, and NY-ESO-1 was evaluable in 31 baseline specimens and 22 paired specimens; paired genomic profiling was evaluable in 12 cases, with paired tumour mutational burden (TMB) in 10 by whole-exome sequencing and 7 by TSO-500. Paired analyses necessarily exclude patients achieving a pathologic complete response (pCR), who have no residual tumour, and most early progressors. Results: pCR was achieved in 11/42 operated patients (26%, 95% CI 15-41). Median follow-up was 87 months (IQR 24-104). Hydronephrosis was the only baseline factor associated with absence of pCR (p = 0.016). Within the operated cohort, pCR was associated with longer recurrence-free survival (log-rank p = 0.017), but the difference in overall survival did not reach significance (p = 0.121). NAC reduced intratumoral FOXP3 (q = 0.001), NY-ESO-1 (q = 0.013), PD-L2 (q = 0.013), and CD3 (q = 0.043) after correction for multiple comparisons, whereas TMB showed no significant change (TSO-500 p = 0.67; WES p = 0.86). No statistically significant association was detected between any baseline immune marker, including PD-L1, and pCR. The mutational landscape was largely concordant before and after NAC. Conclusions: This study was exploratory and was not powered to validate predictive biomarkers. In this long-term cohort, dd-MVAC was associated with measurable depletion of intratumoral immune populations in chemoresistant tumours, while paired genomic profiles remained broadly concordant. No pre-treatment biomarker identified platinum-refractory patients, but the small evaluable subsets mean these are hypothesis-generating rather than negative findings, and prospective studies with pre-specified biomarker endpoints are required.

chemoresistance↗

PubMed1975

Soluble tumour-specific antigen and its relationship to tumour growth.

Hooded rats bearing a syngeneic methylcholanthrene-induced tumour were evaluated for extent of in vivo host immunity and this was correlated by in vitro techniques with the levels of circulating tumour antigen and specific antibody. Early tumour growth was associated with detectable immunity, as measured by the capacity of the animal to reject a second direct challenge of the same tumour at a remote site. Radioimmunoassay for circulating tumour antigen and indirect membrane immunofluorescence for antitumour antibody did not detect either component at this stage. Animals with advanced tumours lost immunity as detected by direct tumour challenge, and this closely coincided with the appearance of rising levels of circulating soluble tumour antigen. Although the host possessed the immunologic ability to react against its own neoplasm, this ability was insufficient to produce tumour rejection. Active immunotherapy initiated at the time of, or up to 10 days after, intramuscular challenge with tumour, increased tumour immunity sufficiently for tumour growth to be prevented. Successful immunization was associated with the early appearance (16 days) of measurable levels of antitumour antibody and absence of circulating antigen. It is concluded that soluble tumour antigen present in the local microenvironment of the tumour in the early stages of tumour growth interferes with the ability of immune cells to cause tumour rejection. As the tumour progressively grows, sufficient soluble antigen is produced and released systemically to suppress the effector arm of the host's tumour immune response at distant sites. The levels of circulating soluble tumour antigen attained may be of critical importance in the suppression of rejection responses that prevent metastasis.

Animals↗

PubMed2024

Understanding the biological processes of kidney carcinogenesis: an integrative multi-omics approach.

Biological mechanisms related to cancer development can leave distinct molecular fingerprints in tumours. By leveraging multi-omics and epidemiological information, we can unveil relationships between carcinogenesis processes that would otherwise remain hidden. Our integrative analysis of DNA methylome, transcriptome, and somatic mutation profiles of kidney tumours linked ageing, epithelial-mesenchymal transition (EMT), and xenobiotic metabolism to kidney carcinogenesis. Ageing process was represented by associations with cellular mitotic clocks such as epiTOC2, SBS1, telomere length, and PBRM1 and SETD2 mutations, which ticked faster as tumours progressed. We identified a relationship between BAP1 driver mutations and the epigenetic upregulation of EMT genes (IL20RB and WT1), correlating with increased tumour immune infiltration, advanced stage, and poorer patient survival. We also observed an interaction between epigenetic silencing of the xenobiotic metabolism gene GSTP1 and tobacco use, suggesting a link to genotoxic effects and impaired xenobiotic metabolism. Our pan-cancer analysis showed these relationships in other tumour types. Our study enhances the understanding of kidney carcinogenesis and its relation to risk factors and progression, with implications for other tumour types.

Kidney Neoplasms↗

PubMed2026

Prognostic significance of NLRP-3 expression in solid cancers: a systematic review and meta-analysis.

BACKGROUND: The inflammasome is a critical immunological sensor comprised of NLRP-3, ASC, and CASPASE-1. Mutations in NLRP-3 are prevalent in inflammatory diseases. However, the role of NLRP-3 in cancer is controversial. This study investigates whether NLRP-3 expression is associated with clinical outcomes in patients with solid cancers. METHODS: PubMed (MEDLINE), Embase, Cochrane, and Google Scholar were searched for articles reporting NLRP-3 expression and disease outcome data in cancer patients. RevMan Review Manager was used to calculate pooled hazard ratios and Mantel-Haenszel pooled odds ratios. RNA sequencing datasets from the TCGA Pan-Cancer (PANCAN) were used for external validation. RESULTS: Patients with higher NLRP-3 expression showed a significant association with larger tumor size, advanced tumor grade, TNM stage, and presence of metastasis. High NLRP-3 expression has a significant association with poor OS (HR:2.12, 95% CI = 1.49-3.03), p < 0.0001) and DFS (HR:1.86, 95% CI = 1.30- 2.65, p = 0.0007). Subgroup analysis showed that higher NLRP-3 expression is associated with worse OS in head and neck cancer (HR: 2.77, 95% CI = 1.88-4.09, p < 0.00001), colorectal cancers (HR:2.14, 95% CI= 1.59- 2.87, p < 0.00001), and pancreatic cancer patients (HR: 3.19, 95% CI = 1.73-5.91, p = 0.0002). CONCLUSION: High NLRP-3 expression is associated with advanced disease and poor outcomes in many solid tumours.

Humans↗

PubMed1978

Effects of sensitizers on cell respiration: III. The effects of hypoxic cell radiosensitizers on oxidative metabolism and the radiation response of an in vitro tumour model.

Physiological factors are important when considering the effects of radiosensitizers on the radiation response of complex systems such as multicellular spheroids. In this system, under conditions of unlimited nutrient supply, cells are rendered hypoxic by metabolism. Thus, using the spheroid system as an in vitro model of the tumour-cell microenvironment, we have determined the relative contribution of radiosensitization and respiratory effects of a number of electron-affinic sensitizers having potential clinical use. These studies are indicative of physiological responses at the cellular level, and suggest optimal drug administration schemes for obtaining maximal radiation response in vivo hypoxic cell sensitizers.

Cell Survival↗

PubMed2025

Axonal injury is a targetable driver of glioblastoma progression.

Glioblastoma (GBM) is an aggressive and highly therapy-resistant brain tumour1,2. Although advanced disease has been intensely investigated, the mechanisms that underpin the earlier, likely more tractable, stages of GBM development remain poorly understood. Here we identify axonal injury as a key driver of GBM progression, which we find is induced in white matter by early tumour cells preferentially expanding in this region. Mechanistically, axonal injury promotes gliomagenesis by triggering Wallerian degeneration, a targetable active programme of axonal death3, which we show increases neuroinflammation and tumour proliferation. Inactivation of SARM1, the key enzyme activated in response to injury that mediates Wallerian degeneration4, was sufficient to break this tumour-promoting feedforward loop, leading to the development of less advanced terminal tumours and prolonged survival in mice. Thus, targeting the tumour-induced injury microenvironment may supress progression from latent to advanced disease, thereby providing a potential strategy for GBM interception and control.

Glioblastoma↗

PubMed2026

BAP1 Loss in Pleural Mesothelioma Is Associated With Reduced Soluble CCL2 in Patient Effusion, Abrogated CCL2-Mediated Monocyte Recruitment In Vitro.

OBJECTIVES: Pleural mesothelioma is an incurable cancer of the cell layer lining the chest wall and lung. Patients frequently present with pleural effusion, which is often drained for symptom relief and enables minimally invasive sampling of the tumour environment, including immune cells and related soluble factors. Most of the mesothelioma tumours exhibit loss of BRCA1-associated protein 1 (BAP1), a multifunctional tumour suppressor protein. Here, we aim to elucidate the effect of BAP1 loss on the mesothelioma microenvironment through profiling soluble factors within pleural effusion. METHODS: A custom panel of 22 soluble factors was measured by Luminex assay and enzyme-linked immunosorbent assay in an initial cohort of 40 patients with known BAP1 status. Validation was performed by enzyme-linked immunosorbent assay in an independent cohort of 100 cases. Secretion of soluble factors and chemoattraction of monocytes were characterised using a CRISPR-mediated BAP1 deletion model in a mesothelioma and a lung cancer cell line. Immune cell infiltration, estimated by CIBERSORT, was further explored in the Cancer Genome Atlas -MESO cohort. RESULTS: Soluble C-C motif chemokine ligand 2 (CCL2) was approximately 55% to 60% lower in pleural effusion from BAP1-loss cases in both independent cohorts. Deletion of BAP1 reduced CCL2 secretion in vitro and abolished CCL2-mediated chemoattraction of monocytes in both mesothelioma and lung cancer cell lines. In the Cancer Genome Atlas -MESO cohort, BAP1-mutant tumours exhibited a reduction in estimated macrophage content. CONCLUSION: Loss of BAP1 impairs CCL2 secretion into pleural effusions, potentially influencing monocyte recruitment into the tumour microenvironment.

BAP1↗

PubMed2026

Putative glioblastoma origin-like cells in the subventricular zone: isolation and characterization.

Glioblastoma (GBM) remains lethal despite maximal therapy. The adult subventricular zone (SVZ), a neural stem-cell niche, has been implicated as a potential site of origin, yet the identity and functional properties of putative GBM origin-like cells (GBM-OCs) within the SVZ remain unclear. An SVZ-restricted somatic mutation mouse model (Cre-induced EGFRvIII expression with Trp53 and Pten disruption) was established and mouse SVZ-derived cells were prospectively isolated for functional and molecular profiling. Self-renewal, multipotency, invasive potential and tumour-initiating capacity were assessed relative to control SVZ cells and matched tumour-derived tumourspheres. Whole-genome and RNA sequencing defined genomic and transcriptional alterations during early progression. Mouse GBM-OCs exhibited self-renewal and multilineage differentiation and initiated tumours only after re-implantation into the SVZ (11/29, 38%), whereas direct striatal implantation failed (0/25, 0%), indicating context-dependent tumorigenic potential associated with the SVZ microenvironment. In contrast, tumour-derived tumourspheres retained tumorigenic capacity upon implantation into both the SVZ and the striatum. During progression from mouse GBM-OCs to tumours, whole-chromosome and arm-level aneuploidies accumulated. In patients with GBM, multi-region single-nucleus RNA sequencing of tumour-free SVZ, matched tumours and tumour-free cortex identified rare neural stem cell-like, astrocyte-like and oligodendrocyte precursor-like SVZ populations transcriptionally aligned with GBM programmes. These cells showed single-nucleus RNA-inferred chromosome 7 gain and/or chromosome 10 loss signals, with concordant low-frequency copy-number alterations in the SVZ detected by exome sequencing and enriched in matched tumours. Together, these findings support the presence of SVZ-resident stem or progenitor-like populations with early GBM-associated features, consistent with putative GBM-OCs, and highlight the SVZ niche as a potential target for early detection and niche-informed therapeutic strategies.

Animals↗

PubMed1976

Tube leukocyte (monocyte) adherence inhibition assay for the detection of anti-tumour immunity. III. "Blockade" of monocyte reactivity by excess free antigen and immune complexes in advanced cancer patients.

Leukocytes from patients with limited cancer display LAI reactivity whereas leukocytes from patients with metastatic cancer frequently demonstrate no reactivity in the tube LAI assay. The leukocytes (monocytes) of reactive patients react with tumour antigen through specific cytophilic anti-tumour IgG antibody bound to the monocyte's Fc cell surface receptors. The non-reactive monocytes from patients with advanced cancer lacked the ability to bind free cytophilic anti-tumour antibody. Moreover, the serum of the non-reactive patient contained no free cytophilic anti-tumour antibody capable of "arming" normal leukocytes. The serum of patients with large tumour burdens contained free tumour antigenic determinants capable of absorbing free cytophilic anti-tumour antibody from the serum of reactive patients or when preincubated with reactive leukocytes abrogating their LAI responsiveness immunologically specifically. Blocking was immunologically specific; therefore, the specificity must reside in the tumour antigenic determinant since immune complexes are bound nonspecifically. The tumour antigen coat was removed by gentle trypsinization of the monocyte's surface. This restored the monocyte's capacity to react with the sensitizing tumour antigen and to bind free cytophilic antibody from the microenvironment. Nonreactivity in the tube LAI assay of patients with metastatic cancer was not the result of a numerical deficit of circulating monocytes but was mediated by an excess of tumour antigen in the microenvironment of the sensitized monocyte.

Adenocarcinoma↗

PubMed2025

Epigenetic orchestration of cancer-immune dynamics: mechanisms, technologies, and clinical advancements.

BACKGROUND: Epigenetic dysregulation plays a pivotal role in cancer immune evasion by orchestrating tumour antigen silencing, immune cell dysfunction, and the formation of an immunosuppressive microenvironment. By disrupting successive phases of the cancer-immunity cycle-from antigen presentation to T cell exhaustion-these aberrations facilitate immune escape and tumour progression, highlighting the need for targeted epigenetic intervention. AIM OF REVIEW: This review systematically dissects how epigenetic alterations impair anti-tumour immunity at each stage of the CI cycle. It not only integrates fragmented mechanistic evidence but also emphasizes underexplored crosstalk between specific epigenetic regulators and immune cell types. It further highlights emerging technologies-such as single-cell epigenomics, spatial multi-omics, and CRISPR-based screens-that are driving discovery of novel therapeutic targets and refining patient stratification. Key scientific concepts of review. We discuss how epigenetic interventions, alone or in combination with immunotherapies, can reinvigorate immune responses and overcome resistance to current treatments. A particular focus is given to how integrative high-resolution platforms are mapping immunoepigenetic landscapes, enabling mechanism-informed, precision immunotherapy strategies. By bridging epigenetic regulation with translational immuno-oncology, this review outlines a future where epigenetic reprogramming becomes central to overcoming immune evasion in cancer.

Humans↗

PubMed1978

[Kinetics of cell proliferation and cancer: introduction (author's transl)].

Research in the kinetics of cell proliferation directly interests oncologists for fundamental and pragmatic reasons. Since cancer is a perturbation of the control of cell proliferation and differentiation, such research may help to understand, the regulation mechanisms, in particular the role of microenvironment, of long range humoral factors, and of membrane site receptors. Furthermore the kinetics of cell proliferation in a normal tissue, or a tumour, influences its response to radiation or drugs. From this evolves the practical interest in research on hemopoietic tissues and on human and experimental tumors. Finally, the growth kinetics of human tumors explain their natural history and opens prospects for the treatment of intraclinical neoplastic disease and metastasis.

Animals↗