Novel Strategies for Cancer Immunotherapy: Targeting Immune-Mediated Suppressive Mechanisms

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Background

Over the past decade, novel forms of cancer therapies, collectively referred to as cancer immunotherapies, have emerged and yielded spectacular results in unfortunately still a minority of cancer patients. Immunotherapies mobilize the immune system to promote or restore effective anti-tumor immune responses. Pioneer approaches targeting the CTLA-4/B7 and PD1/PDL1 immune checkpoint axes have now reached broad clinical applications. Such treatments often yield sustained benefits, but strong responses are observed in only a minority of treated patients, whereas resistance to immune checkpoint inhibitors (ICIs) is observed in a substantial fraction of patients. Primary or acquired resistance to ICIs are common, making it difficult to identify predictive markers of efficacy or resistance. Major efforts are therefore being made to identify new targets that activate, unleash or enhance antitumor immune responses.

In this context, the targeting of the immunosuppressive tumor microenvironment (TME) is of strong interest and a current challenge is to decipher at molecular and cellular levels the immunosuppressive mechanisms that contribute to primary or acquired resistance of cancer cells to anti-tumor immune responses, and to provide proof-of-concept of efficacy for novel forms of therapies that target these mechanisms. A better understanding of the relationships between cancer cells and immune cells is required to develop novel strategies to improve the outcome and increase the proportion of patients responding to cancer immunotherapy. For example, Tregs are modulators of adaptive immune responses and play a role in the tolerance initiation to self-antigens, providing through various suppressive mechanisms a favorable environment to tumor development. Nevertheless, due to Treg subpopulation diversity and the existence of other regulatory cell types, investigations are required to better understand relationships between tumor and non-tumor cells within the tumor microenvironment to identify new therapeutic targets to achieve effective anti-tumor immunity.

The aim of this Research Topic is to provide a comprehensive overview of immunosuppressive mechanisms that seem to prevail within the tumor microenvironment as well as the identification of new immunosuppressive mechanisms. We welcome authors to submit Original Research and Review articles revolving around the following three main axes:

i) Inhibitory receptors expressed by cytotoxic lymphocytes
ii) Suppressive immune cells and their related mechanisms (e.g. Tregs, myeloid cells)
iii) Immunosuppressive mechanisms shared by tumor and immune cells (CD47/SIRP, CD39/CD73, and RANK)
iv) Therapeutic strategies to target the TME for the immunotherapy of cancer

Dr. Nathalie Bonnefoy is co-founder and shareholder of OREGA Biotech. The other Topic Editors declare no competing interests with regard to the Research Topic subject.

Keywords: tumor environment, immunotherapy, immunosuppression, regulatory cells, tumor escape

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