PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Lymphocytes, Tumor-Infiltrating”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources
PubMed1992

Genetic modification of a murine fibrosarcoma to produce interleukin 7 stimulates host cell infiltration and tumor immunity.

Retroviral-mediated gene transfer was used to introduce and express the gene for murine interleukin 7 (IL-7) in a fibrosarcoma tumor (FSA). The tumorigenicity of these genetically modified FSA cells was greatly decreased in immunologically intact syngeneic mice but was unaltered in T-cell-deprived mice. IL-7-infected tumors that did grow in intact animals from large size inocula did so slowly and had a high incidence of spontaneous regression. Furthermore, mice that had rejected tumors became specifically immune to challenge with uninfected parental tumor cells. IL-7-infected FSA growing in intact mice were heavily infiltrated with host T-cells that were presumably responsible for slow growth and tumor regression, and tumor cells were in the minority. Fluorescence-activated cell sorter analysis showed that there was a 530% increase in T-cells in IL-7-infected FSA compared with control tumors. CD8+ T-cells were particularly elevated, but CD4+ lymphocytes were also increased in number, as were eosinophils and basophils. The CD4+:CD8+ ratio in IL-7-infected FSA was 1:1.7 in comparison to 1:0.6 in control tumors. Lymphocytes isolated from IL-7-producing tumors had greatly enhanced cytotoxicity towards uninfected, parental FSA cells. Killing of non-cross-reacting fibrosarcoma line was also increased but to a much lesser extent. Injection of recombinant human IL-7 directly into established FSA tumors slowed their growth and, in a significant number of instances, caused complete regression. Mice that had rejected tumor became specifically immune. The dose that was needed for this effect was, however, somewhat large: 20 micrograms twice daily for 10 days. This result contrasts with the efficacy of IL-7 gene infection in stimulating responses to the same tumor. These considerations make IL-7 a good candidate for tumor-directed cytokine gene therapy.

Animals↗
PubMed1992

Prospects for human gene therapy.

Retroviral vectors containing marker genes and the sequence for human proteins have been used to transduce cultured lymphocytes, which have then been reinfused into patients. Circulating hematopoietic progenitor cells from human fetal cord blood obtained at the time of term and premature deliveries as early as 19 weeks of gestation have been shown to express such transduced genes in vitro. Cord blood cells from fetal sheep sampled and transduced ex vivo and transfused back in utero expressed marker genes up to two years after birth. Although the efficiency of gene transfer into cells and their long-term expression need to be improved, the potential exists for treating some genetic diseases after prenatal diagnosis either in utero or shortly after birth.

Animals↗
PubMedDate not supplied

Postoperative adjuvant immunochemotherapy and infiltration of dendritic cells for patients with advanced gastric cancer.

To determine the group of patients for whom a biological response modifier is useful, the efficacy of postoperative adjuvant immunotherapy was investigated with regard to infiltration of dendritic cells (DC) in patients with advanced gastric cancer who underwent absolute curative resection. The infiltration of DC was classified into marked and slight. The chemotherapy group was prescribed mitomycin C and tegafur, while for the immunochemotherapy group a biological response modifier, PSK, was also prescribed in survival between the chemotherapy and immunochemotherapy groups. In patients with slight infiltration, however, the 5 - year survival rates were 0% in the chemotherapy and 15% in the immunochemotherapy group. Patients given PSK survived longer than those given chemotherapy only (P less than 0.05). Therefore, adjuvant immunotherapy may be considered for patients with advanced gastric cancer with slight infiltration of DC.

Adjuvants, Immunologic↗
PubMedDate not supplied

Large scale expansion of human tumor infiltrating lymphocytes with surface-modified stimulator cells for adoptive immunotherapy.

Expansion of tumor infiltrating lymphocytes (TIL) in vitro is hampered by several factors, including a limited amount of lymphocytes obtained from different tumors, unknown target antigens and limited supply of antigen-presenting cells (APC) which are generally believed to be essential in the classical way of T cell stimulation and expansion. In approaching these difficulties, we have recently used surface-oxidized allogeneic PBL to stimulate the TIL periodically in the presence of a low dose of rIL-2 (200 IU/ml). TIL derived from 22 (out of 23) tumor specimens could be expanded with 20 -10(7) fold increases over 6-16 weeks to a sufficient amount of 10(9) -10(11) cells for adoptive immunotherapy. In contrast, only 2-100 fold increase were observed in six tumor specimens (out of 23) when 200 IU/ml rIL-2 was used only. The phenotypes, autologous tumor reactivity and cytolytic capability of TIL propagated with surface-oxidized stimulators were similar to those expanded in the presence of IL-2 alone. These data suggest that expanding TIL with surface-modified stimulator cells could be a useful alternative method to obtain a large amount of tumor specific cytolytic T cells for clinical immunotherapeutic use, irrespective of tumor-antigen stimulation and MHC restriction.

Breast Neoplasms↗
PubMed1992

Immunology of the bladder.

Immunobiology techniques that once were the domain of research are increasingly being applied in the clinic. Transitional epithelium of the bladder undergoes some recognized immunologic changes as it becomes malignant, and their detection may have prognostic value. Examples of such changes are deletion of the ABO(H) blood group antigens, inappropriate expression of Lewis antigens, loss of beta-2 microglobulin and the MHC class 1 heavy chain, and alterations in the production of cellular adhesion molecules and integrins. Other possibly useful markers are ras oncogene products, Thomsen-Friedenreich antigen, epidermal growth factor receptor, and perhaps antigens unique to transitional-cell carcinoma.

Antigens, Neoplasm↗
PubMed1991

Immunology of hepatocellular carcinoma.

The immune surveillance theory continues to remain a powerful force in cancer research and therapy despite the varying degrees of enthusiasm from both its supporters and critics. The role of both specific and non-specific immune responses in the host's defense against hepatocellular carcinoma is presented as well as the possibilities of immune-system manipulation for the prevention and therapy of this tumour.

Antibodies, Monoclonal↗
PubMed1990

[Study on the mechanism of tumor regression by adoptive immunochemotherapy in mice].

The mechanism of tumor regression by adoptive immunochemotherapy has been unknown. We examined tumor infiltrating lymphocytes (TILs) and cytokines, using immunohistochemical staining and the histo in situ hybridization (HISH) technique, on Meth A tumor in regression of BALB/c mice. In addition, we examined cytokine activity in the serum of mice with a tumor in regression. The result of immunohistochemical staining showed that the number of Thy-1+ cells, Lyt-1+ cells, OKIa1+ cells all increased in the tumors in regression compared to those in the tumors in non-regression. However, there were no these TILs in the necrotic part of tumor. This result suggested that TILs released substances which might include cytokines. A small number of each cytokine mRNA was observed, using HISH with cytokine DNA probes. TNF-alpha, and -beta mRNA were observed in both he tumors in regression and non-regression; while, IFN-beta and -gamma mRNA were observed only in the tumor in regression. TNF-alpha activity in the serum of tumor in regression group was higher than that of he tumor in non-regression group. IFN activity in the serum of the tumor in regression group started increasing after adoptive immunochemotherapy. These results show that cytokines as well as TILs have important roles in tumor regression.

Animals↗
PubMed1991

Immunotherapy of malignant melanoma.

The growth of melanoma in humans depends not only on the malignant potential of the tumor but also on the patient's immune response to the melanoma. As a result, a variety of strategies have evolved to treat melanoma by stimulating antitumor immune responses to melanoma. This article reviews the different approaches being taken and the results obtained to date.

Antibodies, Monoclonal↗
PubMedDate not supplied

Selective usage of TCR V beta in tumor-specific CTL lines isolated from ovarian tumor-associated lymphocytes.

We have developed a series of six CTL lines exhibiting preferential killing of autologous tumour cells from tumour-associated lymphocytes (TALs) infiltrating malignant ovarian ascites. Five out of six CTL lines showed increased percentages of V beta 8.1+ cells, four showed increased percentages of V beta 5.3+ cells and one showed increased percentages of V beta 6.7+ cells. On the contrary, fresh isolated TALs or autologous PBMCs, when stimulated by OKT3 mAb or other TAL cultures with nonspecific cytolytic function, did not show preferential usage of any of these families. Most important, V beta 8.1+ and V beta 6.7+ T cells within the CTL-TALs mediated cytoxicity against autologous targets. This represents the first demonstration of preferential usage of TCR V beta in ovarian tumor-specific CTLs and suggests possible association between tumor surveillance and TCR V beta genes.

Cell Line↗
PubMed1992

Engraftment of human peripheral blood leukocytes into severe combined immunodeficient mice results in the long term and dynamic production of human xenoreactive antibodies.

Severe combined immunodeficient (SCID) mice engrafted with human peripheral blood leukocytes (hu-PBL-SCID) represent a potentially important small animal model for the study of human immune function. Attempts to generate human primary immune responses to exogenous Ag in the hu-PBL-SCID have had limited success which raises questions about the functional capacity of human lymphocytes in the SCID environment. Here, we demonstrate that the spontaneously secreted human Ig in hu-PBL-SCID includes antibodies with specificity for several different mouse RBC (mRBC) proteins. These antibodies apparently reflect the transfer of peripheral B cells which are responsible for the production of naturally occurring xenoreactive antibodies in the donor. Western blot analysis showed that engraftment of anti-mRBC specificities was random among mice receiving PBL from the same donor sample. In at least one mouse, this engraftment was polyclonal and included human IgM and IgG which recognized at least 12 different mRBC proteins ranging in size from 35 to > 200 kDa. Anti-mRBC specificities were found to vary with time demonstrating a dynamic expression of the human xenoreactive repertoire in hu-PBL-SCID. In contrast to mice engrafted with human PBL, mice engrafted with another source of human B cells, i.e., tumor-infiltrating leukocytes, produced very little or no human anti-mRBC antibody. Ag-driven proliferation of xenoreactive clones may result in a skewing of the engrafted human B cells in hu-PBL-SCID which could account in part for the limited ability of hu-PBL-SCID to respond to exogenous Ag. The long term production of anti-mRBC antibodies and the modulation of the expressed xenoreactive repertoire observed in hu-PBL-SCID represents an opportunity to study the molecular genetics and cell biology of the human humoral immune response to a defined complex Ag.

Adsorption↗
PubMed1991

Special subtypes of pulmonary adenocarcinomas indicated by different tumor cell HLA-expression and stromal infiltrates. A light, electron microscopic and immunohistologic study.

A total of 31 human peripheral adenocarcinomas (AC) of the lung were subclassified by light and electron microscopy according to their phenotypic characteristics. The expression of HLA-A,B,C and HLA-DR on tumor cells, and the degree of subclassified mononuclear cell infiltration were determined using immunohistologic and morphometric methods. The study shows that pulmonary AC can be subdivided in two main types with different properties. The first type is characterized by mucin production comparable to that of bronchial goblet cells. These mucinous AC of type I show nearly no expression of HLA-DR; the tumor volume fraction with HLA-A,B,C expression is greatest in highly differentiated AC I, and decreases significantly with lower grades of differentiation. The AC of type II, possibly originating from the bronchioloalveolar transitional zone, show properties of Clara cells and of type II-pneumocytes by light and electron microscopy. These features include apically located electron-dense granules and lamellar bodies occurring often simultaneously. Both groups of HLA-antigens, HLA-A,B,C and HLA-DR, are homogeneously distributed in a similar phenotypic fashion to Clara cells and pneumocytes II of the normal lung. The significant differences in mononuclear cell infiltration between the two tumor types are possibly induced by the different HLA-DR expression, which have not been seen in AC from other sites. In AC II with homogeneous HLA-DR expression in the tumor epithelium, the numbers of tumor-infiltrating Langerhans cells, and T- and B-lymphocytes are significantly higher than in AC I, possibly indicating better host immunologic defense mechanisms against these tumors.

Adenocarcinoma↗
PubMed2026

MIF-CD74 axis facilitates MDSC infiltration in the tumor microenvironment of pancreatic ductal adenocarcinoma.

Immune checkpoint inhibitors show insufficient efficacy against pancreatic ductal adenocarcinoma (PDAC). The tumor microenvironment (TME) has a remarkable influence on responsiveness to cancer immunotherapy. The aim of this study was to investigate immunosuppressive characteristics of TME in PDAC tissues. The flow cytometry (FCM) of PDAC surgical specimens revealed that the profile of tumor-infiltrating leukocytes was classified into myeloid cell- and T-cell-dominant subtypes; the myeloid subtype was associated with poorer patient outcomes. Myeloid-derived suppressor cells (MDSCs) showed the highest hazard ratio among various myeloid cell types. Single-cell RNA sequencing and FCM revealed that most MDSCs, but not lymphocytes, in PDAC tissues characteristically express CD74. Macrophage migration inhibitory factor (MIF), a CD74 ligand, was highly expressed in cancer-associated fibroblasts (CAFs) and cancer cells. Spatial transcriptomics demonstrated that the MIF-CD74+ myeloid cell interaction was recognized in CAF-dominant areas in PDAC tissue. CAFs expressing immune suppressor molecules such as MFAP5 and LRRC15 were consistent with MIF+ CAFs. Furthermore, MIF+ CAFs enhanced the migratory activity of MDSCs and promoted MDSC induction and activation. In the murine model, MDSCs were significantly increased in MIF-expressing PDAC tumors, as were CD74+ M-MDSCs per M-MDSC, confirming in vivo interaction between CD74 and MIF. MDSCs play a crucial role in creating an immunosuppressive TME in PDAC; the MIF-CD74 axis drives interactions between MDSCs and CAFs.

Humans↗
PubMed2026

In vivo genome-wide CRISPR screens identify FOXR1 as a suppressor of CD8+ T cell antitumor immunity.

T cell dysfunction critically limits the efficacy of T cell-based immunotherapies in solid tumors, yet the intrinsic regulators of T cell dysfunction remain incompletely understood. Through an in vivo genome-wide CRISPR screen in tumor-infiltrating CD8+ T cells, we identified Forkhead Box R1 (FOXR1) as a potent transcriptional suppressor of CD8+ T cell effector functions. Genetic ablation of FOXR1 significantly enhanced cytokine production and cytotoxic capacity in both murine and human CD8+ T cells, whereas its overexpression impaired T cell activation and effector molecule expression. Mechanistically, multiomics integration of RNA-seq, CUT&Tag-seq, and ATAC-seq revealed that FOXR1 binds directly to promoter regions of key effector genes, including IL2, GZMB, and PRF1, and represses their expression. Importantly, FOXR1 deletion in human anti-CD19 CAR T cells improved their efficacy against solid tumors, demonstrating that FOXR1 is a checkpoint of T cell effector function and targeting FOXR1 is a promising strategy to enhance CAR T cell efficacy against solid tumors.

Animals↗
PubMed1991

Functional evaluation of tumor-infiltrating mononuclear cells. Detection of endogenous interferon-gamma and tumor necrosis factor-alpha in human colorectal adenocarcinomas.

Quantitative evaluation of the levels of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in the extracts of tumors and their corresponding normal tissues resected from 43 patients with colorectal adenocarcinoma was done using solid-phase, sandwich radioimmunoassay. The levels of both IFN-gamma and TNF-alpha detected in the tumor tissues were higher than those in the corresponding normal colorectal tissues obtained from each patient. A significant negative correlation was observed between the level of IFN-gamma and TNF-alpha in each tumor extract. The decrease of the level of IFN-gamma in the tumor correlated with the advance of clinical stage, and the levels of IFN-gamma of the patients with distant metastases were significantly lower than those of the patients without distant metastases. However, an increase in the level of TNF-alpha correlated not only with an enlarged diameter but also with the extent of the primary tumor. Immunohistochemical staining of IFN-gamma and TNF-alpha producing cells in tumor tissues showed that IFN-gamma was mainly produced by CD4+ CD8- T-lymphocytes and TNF-alpha was mainly produced by CD11c+ cells with macrophage-like morphology. These results suggest that CD4+ T-lymphocytes that produce IFN-gamma might play an important role in the antitumor response against cancer progression in human colorectal adenocarcinomas.

Adenocarcinoma↗
PubMed2026

A Phase II Feasibility Study Combining Pembrolizumab and Metformin in Patients with Metastatic Head and Neck Cancer.

PURPOSE: Survival for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) remains low with <20% immunotherapy response. Metformin increases tumor-infiltrating CD8+ T and natural killer (NK) cells, which harbor PD-1. In this phase II clinical trial (NCT04414540), we combined metformin and pembrolizumab to evaluate the overall response rate (ORR) in R/M HNSCC and assess NK-cell activity. PATIENTS AND METHODS: Eligible patients were randomized 1:1 into two arms: (i) metformin extended-release (ER) dose escalation to 2,000 mg over 14 days followed by combination with pembrolizumab 200 mg every 3 weeks or (ii) pembrolizumab 200 mg every 3 weeks followed by combination with metformin ER 2,000 mg daily. The primary endpoint was ORR per RECIST 1.1. Nineteen evaluable patients were planned to estimate the proportion of approximately 32% ORR. Safety was evaluated according to Common Terminology Criteria for Adverse Events v5.0. The distribution, activation, and cytotoxic function of NK cells were analyzed via flow cytometry. RESULTS: Twenty-one patients were enrolled; 76% were male, 52% were smokers, and the median age was 64 years. Ten patients had oropharyngeal tumors, of which nine were p16+. Eighteen patients were evaluable for response, including four complete and five partial responses for an ORR of 50% [95% confidence interval (29-71)]. Combination therapy was well tolerated with no unexpected adverse events (AE). Five grade 3 AEs occurred: nausea, diarrhea, fatigue, and weight loss. Metformin led to increased peripheral NK-cell maturation and cytotoxic ability. CONCLUSIONS: The combination of metformin and pembrolizumab was well tolerated with mild gastrointestinal AEs and promising activity, warranting further investigation in a randomized trial.

Humans↗