The expression of MHC class II molecules on murine breast tumors delays T-cell exhaustion, expands the T-cell repertoire, and slows tumor growth

AbstractThe expression of MHC class II molecules (MHCII) on tumor cells correlates with survival and responsiveness to immunotherapy. However, the mechanisms underlying these observations are poorly defined. Using a murine breast tumor line, we showed that MHCII-expressing tumors grew more slowly than controls and recruited more functional CD4+ and CD8+ T cells. In addition, MHCII-expressing tumors contained more TCR clonotypes expanded to a larger degree than control tumors. Functional CD8+ T cells in tumors depended on CD4+ T cells. However, both CD4+ and CD8+ T cells eventually became exhausted, even in MHCII-expressing tumors. Treatment with anti-CTLA4, but not anti-PD-1 or anti-TIM-3, promoted complete eradication of MHCII-expressing tumors. These results suggest tumor cell expression of MHCII facilitates the local activation of CD4+ T cells, indirectly helps the activation and expansion of CD8+ T cells, and, in combination with the appropriate checkpoint inhibitor, promotes tumor regression.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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Infectious diseases are still a significant cause of morbidity and mortality worldwide. Despite the progress in drug development, the occurrence of microbial resistance is still a significant concern. Alternative therapeutic strategies are required for non-responding or relapsing patients. Chimeric antigen receptor (CAR) T cells has revolutionized cancer immunotherapy, providing a potential therapeutic option for patients who are unresponsive to standard treatments. Recently two CAR T cell therapies, Yescarta® (Kite Pharma/Gilead) and Kymriah® (Novartis) were approved by the FDA for the treatments of certain types ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Authors: Donnenberg AD, Luketich JD, Donnenberg VS Abstract INTRODUCTION: We compared the secretome of metastatic (non-small cell lung cancer (NSCLC)) and primary (mesothelioma) malignant pleural effusions, benign effusions and the published plasma profile of patients receiving chimeric antigen receptor T cells (CAR-T), to determine factors unique to neoplasia in pleural effusion (PE) and those accompanying an efficacious peripheral anti-tumor immune response. MATERIALS AND METHODS: Cryopreserved cell-free PE fluid from 101 NSCLC patients, 8 mesothelioma and 13 with benign PE was assayed for a panel of 40 cytok...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Authors: Grobbelaar C, Ford AM Abstract Acute lymphoblastic leukaemia (ALL) is the most common cancer of childhood. Although the overall survival of children with ALL is now more than 90%, leukaemia remains one of the leading causes of death from disease. In developed countries, the overall survival of patients with ALL has increased to more than 80%; however, those children cured from ALL still show a significant risk of short- and long-term complications as a consequence of their treatment. Accordingly, there is a need not only to develop new methods of diagnosis and prognosis but also to provide patients with le...
Source: Journal of Oncology - Category: Cancer & Oncology Tags: J Oncol Source Type: research
Condition:   Immunotherapy Intervention:   Drug: olaparib, durvalumab, tremelimumab Sponsors:   Centre Georges Francois Leclerc;   AstraZeneca Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conclusions: In our exploratory study of stage III and IV NSCLC patients with CAO, addition of PDT demonstrated hazard of mortality comparable to radiation + chemotherapy group. However, addition of non-PDT ablation showed higher mortality compared to the radiation + chemotherapy group. Future studies should investigate the efficacy and effectiveness of multimodal therapy including radiation, chemo, immunotherapy and bronchoscopic interventions. PMID: 31737325 [PubMed]
Source: Journal of Thoracic Disease - Category: Respiratory Medicine Tags: J Thorac Dis Source Type: research
Bacillus Calmette-Guerin (BCG)-refractory high-grade non –muscle-invasive bladder cancer remains a challenging problem. Radical cystectomy is standard of care, but carries significant morbidity. Therefore, there is a need for effective treatments. Previous salvage intravesical therapies have had disappointing results with long-term follow-up; however, a wide array of novel agents is currently under investigation. These include novel combinations of existing intravesical agents, novel modes of delivery such as hyperthermia, viral mediated therapies, and immunotherapy. We review the need for novel treatment with existi...
Source: Urologic Clinics of North America - Category: Urology & Nephrology Authors: Source Type: research
Due to significant risks of cancer recurrence and progression, and limited options after intravesical Bacillus Calmette Guerin (BCG) therapy, there is a critical unmet need to identify novel treatments for those patients with BCG-unresponsive bladder cancer. There is active investigation of immunotherapies which provide both biologic and clinical rationales for indoleamine-2,3- dioxygenase inhibitors in salvage therapy for non-muscle invasive bladder cancer.
Source: Urologic Clinics of North America - Category: Urology & Nephrology Authors: Source Type: research
This article provides a comprehensive review of the available data for immunotherapy being used as a salvage treatment in non –muscle-invasive bladder cancer. The literature demonstrates that the immune system has an important role in bladder cancer progression. Initial results from studies using checkpoint inhibitors, recombinant interferon-α2b protein, and oncolytic adenoviruses have shown promising responses with acc eptable toxicities. However, the majority of the current data arises from small trials with limited follow-up. There are currently several ongoing studies in this setting, which we await complet...
Source: Urologic Clinics of North America - Category: Urology & Nephrology Authors: Source Type: research
Despite the 40-year reign of bacillus Calmette-Gu érin (BCG) as the most effective immunotherapy in urologic cancers, a lack of clinical tools to predict treatment response has hampered progress in the field. Acting as an immunostimulatory agent against a multitude of phenotypically diverse non–muscle-invasive bladder cancers, response to BCG li kely depends on both tumor characteristics as well as host factors. With a deeper understanding of the tumor biology as well as the mechanism of action underpinning immunotherapy, newer and more effective clinical tools are being constructed to improve patient selection.
Source: Urologic Clinics of North America - Category: Urology & Nephrology Authors: Source Type: research
The best predictors of response to intravesical immunotherapy are tumor grade and stage, tumor recurrence pattern, nomograms, panels of urinary cytokines, and fluorescent in situ hybridization patterns of urine cytology examinations. Future investigations on predictors of Bacillus Calmette-Gu érin efficacy are needed to better select those patients who will really benefit from a conservative treatment. Hardly any of the proposed nomograms were designed to precisely predict the outcome of Bacillus Calmette-Guérin immunotherapy. A new nomogram for NMIBC recurrence and progression based o n all non–muscle-...
Source: Urologic Clinics of North America - Category: Urology & Nephrology Authors: Source Type: research
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