Chemotherapy is much more effective in immunocompetent mice than in immunodeficient ones, and it is now acknowledged that an efficient immune system is necessary to optimize chemotherapy activity and efficacy. Furthermore, chemotherapy itself may reinvigorate immune response in different ways: by targeting cancer cells through the induction of cell stress; the release of damage signals and the induction of immunogenic cell death; by targeting immune cells; inhibiting immune suppressive cells and/or activating immune effector cells; and by targeting the host physiology through changes in the balance of gut microbiome. All these effects acting on immune and non-immune components interfere with the tumor microenvironment, leading to the different activity and efficacy of treatments. This article describes the correlation between chemotherapy and the immune changes induced in the tumor microenvironment. Our ultimate aim is to pave the way for the identification of the best drugs or combinations, the doses, the schedules and the right sequences to use when chemotherapy is combined with immunotherapy.
Most head and neck squamous cell carcinomas (HNSCCs) are caused by lifestyle, such as cigarette smoking, or by viruses, such as human papillomavirus (HPV) and Epstein–Barr virus (EBV). HNSCC remains a clinical challenge, notwithstanding the improvements observed in the past years, involving surgery, radiotherapy, and chemotherapy. Recurrent/metastatic (R/M) disease represents an unmet clinical need. Immunotherapy has improved the prognosis of a small proportion of these patients, but most still do not benefit. In the last decade, several preclinical and clinical studies have explored the HNSCC tumor immune microenvironment (TIME), identifying important differences between smoking-associated and virus-associated HNSCCs. This review aims to present how different etiologies affect the HNSCC TIME, affecting immune escape mechanisms and sensitivity to immunotherapy.
Background Among the risk factors for SCC-HN, smoking is still the most important today. Several studies agree on the effect of smoking on tumor microenvironment while the definition of former smokers and the time of smoking cessation on biologic effect differs among papers. Summary There is evidence that smoker patients have a poorer prognosis than never smokers and former smokers. Translational studies show a relationship between smoking status and gene expression and support the importance of smoking cessation, for instance, demonstrating an inverse relationship between TILs and smoking. Key Messages. Convincing data suggest that quitting smoking at any time may improve patient outcomes. We advocate smoking cessation also after cancer diagnosis.
Malignant mesothelioma (MMe) is a rare neoplasm with few therapeutic options available. The landscape of effective therapy for this disease remained unchanged in the last two decades. Recently, however, the introduction of Immune Checkpoint Inhibitors (ICIs) led to small, but nevertheless, promising improvements. However, many efforts are still needed to radically improve the prognosis of MMe. In this review, we analyze all those therapeutic strategies for MMe that are still in a preclinical or early clinical phase of development. In particular, we focus on novel antiangiogenic drugs and their possible combination with immunotherapy. Furthermore, we describe also more complex strategies such as microRNA-loaded vectors, oncolytic viruses, and engineered lymphocytes.
Background: Immunotherapy of head and neck cancer induces a limited but reproducible rate of long-term survivors, at the cost of treating a large number of patients exposed to toxicity without benefit, regardless of PD-L1 expression.
Therefore, identification of better markers for response is an unmet need.
Materials and methods: 18 cytokines and 24 subpopulations of immune cells, selected on their prevalent Th1 or Th2 effect, were collected from peripheral blood. Samples were gathered at baseline (T0) and after 3 courses of nivolumab (T1) in 22 head and neck cancer patients, refractory to platinum containing therapy or in second line treatment for relapsed/metastatic disease. Data extracted at each time point have been linked to overall survival.
A threshold value able to discriminate between good or poor survival, have been identified by ROC analysis. The relative value of the most promising cytokines/immune cells was determined by PCA.
Results: at T0, 4 cytokines (IL-6, IL-8, IL-10, TGF-β) and 2 immune cells (CD3+ CD8+ LAG3+, CD3+CD11+HLA-DRlowCD14-) were able to discriminate between good and poor survival and allowed the identification of two clusters of patients.
Conclusion: with the limitation of an exploratory analysis, this report suggests that a mixed profile of cytokine and immune cells determined at baseline, is potentially able to discriminate between patients who will benefit from nivolumab treatment and those who will do not.
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