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At least 19 recordsLinked to original sources
PubMed1976

Experimental studies of tumor immunotherapy. II. Tumor immunotherapy following tumor extirpation.

In order to approach human cancer immunotherapy, the author carried out the immunotherapy with BCG on mice having homotransplanted cancer, observed the posttransplantation results with lapse of time, conduced daily macrophage inhibition test (MI test) and found the immunotherapy to be effective. At the same time the MI test proved to be a useful criterion in determining the course of cancer progress and effectiveness of the immunotherapy.

Animals↗
PubMed2026

An oxidative stress - and immunotherapy-related six-gene signature defines immune subtypes and predicts prognosis and immunotherapy response in hepatocellular carcinoma.

BACKGROUND: Oxidative stress and the tumor immune microenvironment jointly shape hepatocellular carcinoma (HCC) progression and response to immunotherapy, yet integrated biomarkers linking these processes are lacking. METHODS: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to identify oxidative stress- and immunotherapyrelated differentially expressed genes (OSIRDEGs). Functional enrichment, weighted gene co-expression network analysis (WGCNA) and LASSO-Cox regression were used to construct a prognostic signature. Consensus clustering, TIDE, CIBERSORT and ssGSEA characterized immune phenotypes. Somatic mutation, copy-number and drug-response data were integrated to assess genomic alterations and drug sensitivity. Expression of model genes was validated by qRT-PCR and western blotting in HCC cell lines. RESULTS: We identified 24 OSIRDEGs enriched in cell-cycle and mitotic pathways. WGCNA intersection yielded 18 module genes, from which a six-gene signature (BUB1B, CDKN2A, CENPE, HMMR, PTTG1, SPP1) was derived. The signature robustly stratified patients into high- and low-risk groups with significantly different progression-free and disease-free survival in both TCGA-LIHC and GSE14520. Based on signature expression, two molecular subtypes were defined, exhibiting distinct survival, immune landscapes and predicted immunotherapy responsiveness. Model genes harbored recurrent alterations and showed significant correlations with anticancer agents. All six genes were upregulated at mRNA and protein levels in metastatic HCC cell lines versus normal hepatocytes. CONCLUSIONS: We systematically explored the landscape of OSIRDEGs in HCC, and proposed a validated six-gene signature that refines prognostic stratification, delineates immunerelevant HCC subtypes and highlights candidate biomarkers for therapeutic selection and mechanistic investigation.

Humans↗
PubMed1979

Adoptive immunotherapy and chemo-immunotherapy in murine L-1210 leukemia and its influence on the kinetics of leukemic proliferation.

Donor allogeneic C57Bl/6 lymphoid cells from peritoneal cavity, lymph nodes, thymus and spleen of immunized and non-immunized mice were used for adoptive immunotherapy of L-1210 ascites leukemia in DBA/2J recipients. Donor effector cells were injected i.p. into leukemic mice which were given a whole-body irradiation in a dose of 300 r X-rays prior to leukemia inoculation. The in vitro cytotoxicity of the effector cells was tested by the LT- and 51Cr-tests. Cytokinetics of leukemia undergoing therapy was followed by impulse-cytophotometry. An adoptive chemo-immunotherapy with the aid of peritoneal or splenic lymphoid cells from immunized donors proved to be most effective. The cells were injected on the second day into recipients inoculated with leukemia on the day 0, and then given on the first day a single i.p. injection of cyclophosphamide in a dose of 50 mg/kg body weight. Under these conditions the secondary disease did not influence therapy and apart from a distinctly prolonged survival there was also noted a number of permanent survivals of leukemia. It was also found that peritoneal and splenic lymphoid cells of immunized donors exhibited most pronounced direct and indirect cytotoxicity against target cells in vitro. In vivo, the effector cells mounted an attack on the L-1210 cells probably at the onset of the G1-phase of the cell cycle.

Animals↗
PubMed1977

[Immunotherapy of warts. Is it an experimental model for cancer immunotherapy?].

The warts produced by virus Papova, provedly cancerous, have immunological characteristics that allow to establish some analogies with cancer. Its immunotherapy is studied with levamisole and by means of a delayed immunity reaction "in situ" with regulated intensity. The level of delayed immunity in the patient with warts is established by quantitative DNCB test, finding that the same is impaired in 60% of men and 87% of women. The levamisol therapy cures 54% of warts. The patients that not cure but improve their delayed immunity level after the treatment with levamisol, are submitted to external application of DNCB, using a concentration calculated on the quantitative test results. With regard to their delayed immunity we introduce a new group of patients: the hiperergic type or reactive to 2,5 microgram of DNCB that cures their warts by the sole action of the test. Once obtained the curve of the distribution of delayed immunity values in the warts population before and after the levamisole therapy, we observe that the first is identical to that of cancer patients. In view of the tight relation among diseases with impaired delayed immunity, such as warts, herpes, aphtas, piodermitis and cancer (residual or postsurgical), we propose the same management, control and immunotherapy for all of them.

Clinical Trials as Topic↗
PubMed1979

Immunotherapy of melanoma.

Malignant melanoma is a disease characterized by clinical evidence of host defense, possibly immunologically mediated. It is a disease which tends to be refractory to both radiotherapy and chemotherapy. Immunotherapy has been used in three phases of the disease. 1. Intralesional immunotherapy with a nonspecific immune adjuvant in patients with local intradermal or soft tissue recurrence. This treatment produces approximately 15% regression of both injected and uninjected lesions, and about 60% regression of injected lesions only. Both clinical and laboratory evidence suggests that this regression is immunologically mediated. 2. Patients with surgical removal of all clinically demonstrable tumor, either primary disease alone or regional node recurrence, active nonspecific, and specific, immunotherapy has been used in an adjuvant setting. There is considerable controversy about the benefits accruing to such immunotherapy, but most large scale prospective and randomized studies have suggested that if benefit does result it is modest in degree and probably cannot be measured in terms of increase in cure rate. 3. Immunotherapy has also been used as a nonspecific active adjuvant to single drug or polychemotherapy in patients with disseminated melanoma. Whereas complete response rate may be slightly increased by this maneuver there is no convincing evidence that immunotherapy markedly increases the total objective response rate to polychemotherapy, and survival is only marginally superior when immunotherapy is added to chemotherapy in this setting. Further studies need to be done with active specific immunotherapy with tumor cell membrane extracts; as an adjuvant in patients with minimal body burden of tumor cells; and to study the inaction between chemotherapy and immunotherapy in this disease. Furthermore, studies of chemically defined fractions of either bacterial cell wall or tumor cell extracts must be evaluated both in terms of their ability to augment cell mediated immune responses in the melanoma patient, and also in terms of their ability to induce objective benefit for the patient. The possible use of immunotherapy in patients with primary melanoma has been briefly explored but needs further study. Possible additive effects with radiotherapy and immunotherapy should also be looked at in this disease utilizing high dose fractions and other new forms of radiotherapeutic technique.

Adjuvants, Immunologic↗
PubMed1978

Surgical adjuvant immunotherapy for colorectal cancer.

One hundred forty-four Wistar-Furth rats in 12 therapeutic groups have been studied in a long-term comparison of the effectiveness of nonspecific immunotherapy with MER (methanol extraction residue) vs active-specific immunotherapy with neuraminidase-modified tumor cells. Six months after surgical adjuvant immunotherapy a 100% improvement in survival was achieved with MER immunotherapy compared to untreated control animals. In addition, the use of MER enhanced the value of active-specific immunotherapy where both modalities were combined in sequence. The predicted value of MER-BCG (Bacillus Calmette-Guerin) for the immunotherapy of solid tumors was borne out by these results suggesting that present ongoing clinical trials of MER as adjuvant therapy for large bowel cancer should prove to be successful if properly controlled. The pattern of survival in these experiments suggests that surgical adjuvant immunotherapy is cytostatic rather than cytocidal, and implies the need for long-term, repeated immunizations.

Adenocarcinoma↗
PubMed1976

Immunotherapy of leukemia.

The data reviewed in this paper indicate that immunotherapy is effective in prolonging remission and survival in acute and chronic leukemia. The acute lymphocytic leukemias may or may not respond to immunotherapy and further work is needed in this area. No studies of immunotherapy in chronic lymphocytic leukemia have been done, but this will be an important area for investigation, since there is often profound immunodeficiency in this disease. The malignant lymphomas are another fertile area for this type of research, since they have a high response rate, tumor-associated immunodeficiency, and at least differentiation antigens if not tumor-specific antigens. The scientific basis for the use of immunotherapy in leukemia includes the demonstration of a relationship of rate and duration of remission and survival to immunocompetence, the demonstration of unique tumor-associated antigens on leukemia cells, and the demonstration of immune responses to these antigens which can be boosted by immunization. At the present time, active nonspecific immunotherapy with BCG and MER and active specific immunotherapy have been proved effective in acute myelogenous leukemia. Careful attention should be given to dose, schedule, route, and so forth. Other types of immunotherapy remain to be explored.

Acute Disease↗
PubMed1978

Active immunotherapy in acute myelogenous leukaemia and the induction of second and subsequent remissions.

One hundred and ninety-one adults with acute myelogenous leukaemia were treated with combination chemotherapy consisting of daunorubicin and cytosine arabinoside (Barts III). Sixty-three patients achieved remission and were admitted to one of 3 trials of active immunotherapy: immunotherapy alone, immunotherapy and maintenance chemotherapy or neither of these. All patients had weekly clinical and blood examination and monthly marrow examination. Reinduction chemotherapy was given as soon as relapse was diagnosed in the marrow. The most striking observation was that immunotherapy was associated with easy and repeated reinduction of remission and marked prolongation of survival after first relapse when compared with immunotherapy plus chemotherapy. The possible reasons for this and the value of immunotherapy are discussed in relation to the third trial still in progress which includes 2 maintenance arms, immunotherapy alone and surveillance only.

BCG Vaccine↗
PubMed2024

Case report: response to immunotherapy and association with the fh gene in hereditary leiomyomatosis and renal cell cancer-associated renal cell cancer.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant syndrome caused by a germline mutation in the fumarate hydratase (FH) gene that manifests with cutaneous leiomyomas, uterine fibroids, and renal cell cancer (RCC). Patients with HLRCC-associated RCC (HLRCC-RCC) have aggressive clinical courses, but there is no standardized therapy for advanced HLRCC-RCC. In this study, we described a case of aggressive HLRCC in a 33-year-old female who exhibited a novel heterozygous germline insertion mutation in exon 8 of the FH gene (c.1126 C > T; p.Q376*). The patient underwent laparoscopic resection of the right kidney, but metastases appeared within 3 months after surgery. Histological staining of the resected tumor revealed high expression levels of programmed cell death-ligand 1 (PD-L1). Therefore, the patient was treated with immunotherapy. The patient achieved a partial response to immunotherapy, and the treatment of metastatic lesions has continued to improve. A thorough literature review pinpointed 76 historical cases of HLRCC-RCC that had undergone immunotherapy. From this pool, 46 patients were selected for this study to scrutinize the association between mutations in the FH gene and the effectiveness of immunotherapy. Our results indicate that immunotherapy could significantly improve the overall survival (OS) of patients with HLRCC-RCC. However, no influence of different mutations in the FH germline gene on the therapeutic efficacy of immunotherapy was observed. Therefore, our study suggested that immunotherapy was an effective therapeutic option for patients with HLRCC regardless of the type of FH germline mutation.

Humans↗
PubMed1978

[Possibilities of immunotherapy in malignant melanoma].

The immune response of malignant melanoma bases on evident humoral and cellular defence mechanisms of the host against his tumor. Of special interest is a defective immune response, developing in the course of the disease. Hence, any immunotherapy aims at an immunostimulation and immunoregulation. Local and systemic nonspecific immunotherapy try to raise an immune response against the tumor by stimulating unspecifically the whole immune system. On the contrary, specific immunotherapy tries to stimulate directly the defence mechanisms against the tumor by transfusion of antisera (passive immunotherapy) and sensitized cells (adoptive immunotherapy) and by immunizing the patient with tumor tissue (active immunotherapy). One of the best ways in therapy of melanoma seems to be the combination of immunotherapy with chemotherapy, as yet employed in BCG and DTIC treatment.

Antigen-Antibody Reactions↗
PubMed1978

Clinical trials of immunotherapy: present status.

This brief review of the more promising clinical trials suggests that immunotherapy is indeed beneficial for selected cancer patients. Because of its limited potency, it should not be used as primary treatment for malignant disease except as local immunotherapy for certain accessible tumors. It is effective for eradication of primary neoplasms of the skin as well as cutaneous metastases of malignant melanoma and breast carcinoma. The most important role for immunotherapy is in combination with other modalities. It may help control occult micrometastases that cause recurrence and death following surgical procedures or irradiation. Results of adjuvant immunotherapy appear promising for malignant melanoma, for carcinoma of the lung, breast, and colon, and for soft-tissue sarcomas. In combination with chemotherapy, immunotherapy appears to prolong remission and survival in acute myelogenous leukemia and in disseminated tumors of the lung and breast. Clearly, immunotherapy is not a panacea for malignant disease, but it could become an important arm in a multimodality attack on cancer.

Breast Neoplasms↗
PubMed2025

Multimodal deep learning for immunotherapy response prediction and biomarker discovery in non-small cell lung cancer.

OBJECTIVE: Immunotherapy has emerged as a promising treatment for advanced non-small cell lung cancer (NSCLC), but accurately predicting which patients will benefit from it remains a major clinical challenge. To address this, we aim to develop a novel multimodal method, DeepAFM, that integrates histopathology, genomic features, and clinical information to predict patient responses to anti-PD-(L)1 immunotherapy. MATERIALS AND METHODS: A total of 93 patients with advanced NSCLC were included in this study. Histopathological whole-slide images were processed using a self-supervised VQVAE2 for representation learning. PCA and K-means clustering were then applied for dimensionality reduction and feature grouping. Key regions of interest were visualized through permutation importance evaluation and color-coding techniques. The extracted histopathological features, along with genomic alterations and clinical variables, were integrated into the DeepAFM multimodal prediction model. RESULTS: The DeepAFM achieved a high predictive performance with an area under the curve (AUC) of 0.77 (95% confidence interval: 0.69-1.00). Attention-based heatmaps revealed that the model could identify critical pathological patterns, genomic mutations, and clinical indicators associated with patient responses to immunotherapy. DISCUSSION: The integration of multimodal data enabled the model to capture complex interactions among pathology, genomics, and clinical characteristics, enhancing the interpretability and predictive power of immunotherapy response prediction. The visualization techniques facilitated the identification of biologically meaningful features and potential biomarkers. CONCLUSION: This study demonstrates the effectiveness of the DeepAFM in predicting responses to immunotherapy in advanced NSCLC. The approach not only improves prediction accuracy but also provides valuable insights for personalized treatment strategies and biomarker discovery.

Humans↗
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↗
PubMed1976

Immunological monitoring and immunotherapy in carcinoma of the lung.

One hundred and seven patients with carcinoma of the lung underwent immunologic testing, and 62 of these patients were randomized to an immunotherapy protocol comparing the effects of Pasteur strain BCG, either alone or combined with allogeneic tumor cells, to the effects of no immunotherapy. Patients with residual disease left at the time of surgery or with metastatic disease at the time of diagnosis showed no increase in survival as a result of this form of immunotherapy. An insufficient number of patients with less advanced disease, in whom we would expect the most beneficial effect, have been entered in this study. In general, we were unable to document substantial effects of immunotherapy on the immunologic parameters tested. Only in recall antigen skin testing was there a statistically significant increase in reactivity in the immunotherapy groups. Tests of general immune status appeared to have a predictive value in monitoring lung cancer patients. Anergic patients had a poorer prognosis than did patients who demonstrated skin test reactivity. Patients with normal percentages of lymphocytes (T cells) forming rosettes with sheep erythrocytes at 29 degrees C were generally normal in other tests of immune competence. In serial studies of rosette formation, all patients who developed recurrent disease had a pattern of depressed or falling rosette values, and these abnormalities occurred an average of 3.1 months prior to clinical detection of recurrence. Patients with large-cell anaplastic carcinoma were found to have a significantly higher incidence of depressed rosette levels than the other histologic types. Both large and small-cell anaplastic patients had significantly depressed lymphocyte proliferation by mitogens and allogeneic cells. Although lung cancer patients have been described as immunologically depressed, they are capable of recognizing tumor-associated antigens. When tested in leukocyte migration inhibition assays with tumor-associated antigens, the majority of the patients in our study were found to be reactive. The use of a 3 M KCl extract of pleural effusion cells from a patient with pulmonary adenocarcinoma has given good reactivity and specificity in lung cancer patients of all histologic types. In addition, these patients have been shown to respond in a mixed lymphocyte/tumor interaction to tumor-associated antigens (Dean, 1976b).

Adenocarcinoma↗
PubMed1977

Human models for cancer active immunotherapy.

In this editorial, the author considers the human models for research on cancer immunotherapy. He distinguishes between trials which have given a direct demonstration of the action of immunotherapy, in which the effect of this treatment has been compared to therapeutic abstention, and those which have shown an indirect proof of its action and in which immunotherapy is compared to chemotherapy of which the effect is known, or in which the combination of chemotherapy and immunotherapy is compared with the same chemotherapy applied alone. The author concludes with methodological and ethical considerations about clinical trials applied to active immunotherapy.

Clinical Trials as Topic↗
PubMed1976

[Effect of immunotherapy on lymphocyte function in acute lymphatic leukemia].

During the immunotherapy children suffered from acute leukaemias will have a significantly higher transformation rate than at the beginning of the immunotherapy. This may be explained by an increase of the immunological competence as well as by an enhanced mobilization of lymphatic cells. Leukaemic blasts used for immunoinduction-therapy will have no higher transformation rates as antigens than those cells never contacted by children. During the immunotherapy an increase of transformation rates may be observed after administering unspecific antigens and in mixed cultures. In a retrospective manner the indication for immunotherapy may be checked again in children with immunotherapy on the basis of the clinical course and evaluation of the cellular immunoreaction.

BCG Vaccine↗