About this Research Topic
Reinvigoration of the anti-tumor immune response by targeting immune checkpoints is under extensive investigation in pre-clinical studies as well as in clinical trials. Despite unprecedented success in the treatment of a wide variety of cancers, immune checkpoint blockade only benefit about 20% of cancer patients. In advanced melanoma and lung cancer patients, CD8 T-cell density in tumor biopsies is one of the best predictors of clinical response to PD-1–targeted therapies. The density and diversity of the immune infiltrate in the tumor microenvironment (TME) has also allowed us to classify tumors into “hot”, rich in T cells and proinflammatory cytokines, and “cold”, characterized by an absence or exclusion of T cells from tumor islets.
“Warming up” these so-called “cold” tumors is a pressing issue. The first challenge for tumors lacking a T cell infiltrate will be to initiate an anti-tumor immune response in a suitable TME, without immunosuppression and immuno-exclusion. Consequently, the second challenge is therefore to limit this immunosuppression driven by the cells of TME (immune, tumor, or stromal cells). To this end, it is crucial to identify treatments that can 1) improve tumor cell immunogenicity/antigenicity, 2) ensure efficient recruitment of effector cells, in particular cytotoxic T-CD8+ lymphocytes, into the tumor core, and 3) lower the level of immunosuppression on effector cells. The identification and understanding of the mechanisms that limit this anti-tumor immune response could lead to the rational identification of new therapies that target tumor “weaknesses” and might increase the efficacy of immune checkpoint blockade.
The therapeutic arsenal used in oncology is vast and the growing interest in immunotherapy presses us to reassess the role of these compounds on the immune system. For example, radiotherapy, targeted therapies, and certain chemotherapies have already shown their capacity to sensitize "cold" tumors to the action of immunotherapy and have therefore been defined as "immunogenic". This Research Topic aims to highlight projects that focus on the sensitization of cold tumors to immunotherapy. Such research leads to the rational suggestion of synergistic therapeutic associations that may decrease resistance to immunotherapy and thus extending its benefit to non-responder patients.
In this Research Topic, we would like to highlight Reviews or Original Research articles on the theme of “cold” tumor sensitization to immunotherapy, and for which synergistic therapeutic associations are identified in connection with a phenomenon of resistance to anti-tumor immunity. Authors will be able to propose papers with a wide range of therapeutic strategies (clinically approved or not) for sensitization to immunotherapy. These might include:
i) Direct stimulation of the immune response:
- Cancer cell immunogenicity and antigen release: Viral therapy, chemo/radio/targeted therapies
- Tumor antigen presentation: cancer and dendritic cell vaccines, TLR/RLR and NLR agonists, cytokines
- Immune cell priming and activation: co-stimulation agonists, cytokines
- Immune cell trafficking: chemoattraction modulators, CAR-T cells strategies, bispecific T cell engagers
ii) Indirect stimulation of immune response:
- TME modulators (CAFs, endothelial cells): anti-angiogenic and anti-fibrogenic therapies
- Immunosuppression modulators: Treg, TAMs or MDSCs targeting agents (including some chemotherapeutic agents), suppressive pathways inhibitors (IDO1, CSF1R).
Please Note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) will not be accepted in any of the sections of Frontiers in Oncology.
“Warming up” these so-called “cold” tumors is a pressing issue. The first challenge for tumors lacking a T cell infiltrate will be to initiate an anti-tumor immune response in a suitable TME, without immunosuppression and immuno-exclusion. Consequently, the second challenge is therefore to limit this immunosuppression driven by the cells of TME (immune, tumor, or stromal cells). To this end, it is crucial to identify treatments that can 1) improve tumor cell immunogenicity/antigenicity, 2) ensure efficient recruitment of effector cells, in particular cytotoxic T-CD8+ lymphocytes, into the tumor core, and 3) lower the level of immunosuppression on effector cells. The identification and understanding of the mechanisms that limit this anti-tumor immune response could lead to the rational identification of new therapies that target tumor “weaknesses” and might increase the efficacy of immune checkpoint blockade.
The therapeutic arsenal used in oncology is vast and the growing interest in immunotherapy presses us to reassess the role of these compounds on the immune system. For example, radiotherapy, targeted therapies, and certain chemotherapies have already shown their capacity to sensitize "cold" tumors to the action of immunotherapy and have therefore been defined as "immunogenic". This Research Topic aims to highlight projects that focus on the sensitization of cold tumors to immunotherapy. Such research leads to the rational suggestion of synergistic therapeutic associations that may decrease resistance to immunotherapy and thus extending its benefit to non-responder patients.
In this Research Topic, we would like to highlight Reviews or Original Research articles on the theme of “cold” tumor sensitization to immunotherapy, and for which synergistic therapeutic associations are identified in connection with a phenomenon of resistance to anti-tumor immunity. Authors will be able to propose papers with a wide range of therapeutic strategies (clinically approved or not) for sensitization to immunotherapy. These might include:
i) Direct stimulation of the immune response:
- Cancer cell immunogenicity and antigen release: Viral therapy, chemo/radio/targeted therapies
- Tumor antigen presentation: cancer and dendritic cell vaccines, TLR/RLR and NLR agonists, cytokines
- Immune cell priming and activation: co-stimulation agonists, cytokines
- Immune cell trafficking: chemoattraction modulators, CAR-T cells strategies, bispecific T cell engagers
ii) Indirect stimulation of immune response:
- TME modulators (CAFs, endothelial cells): anti-angiogenic and anti-fibrogenic therapies
- Immunosuppression modulators: Treg, TAMs or MDSCs targeting agents (including some chemotherapeutic agents), suppressive pathways inhibitors (IDO1, CSF1R).
Please Note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) will not be accepted in any of the sections of Frontiers in Oncology.
Keywords: "Cold" tumors, Immmunotherapy, Immune checkpoint, CD8 T cell response, Myeloid and lymphoid suppresive cells, Immunogenic drugs
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
