About this Research Topic
Cancer immunotherapy has been developed during past few decades. Notably, immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 and CTLA-4 have now become one of the standard drug therapies for several cancers. Engineered T cell therapies such as TCR-T therapy and CAR-T cell therapy also attract attention in this field because of the success of CD19 targeted CAR-T cell therapy in B cell lymphoma. A key feature of cancer immunotherapy is the highly durable tumor response, resulting in a plateau of the survival curve. Despite the potential of this type of therapy, the remarkable responses to ICIs are limited to a fraction of patients. Responses to engineered T cell therapy in patients with solid tumors also remain sporadic and transient presumably due to the distinct microenvironment of solid tumors.
Several mechanisms of resistance to ICIs are proposed; lack of suitable neo-antigens, impaired presentation of tumor antigens, metabolic/inflammatory mediators, immune suppressor cells, inhibitory signals via alternate immune checkpoints, and severe T cell exhaustion. Regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) are major immune suppressor cells which inhibit antitumor immune responses. Both high infiltration of Tregs in tumor tissues and high frequency of circulating MDSCs are associated with poor responses to ICI treatment, suggesting these immunosuppressive cells may play a key role in resistance to ICI therapy as well as a predictive response marker. Cancer-associated fibroblasts (CAFs) can represent a complex barrier to entry and activity of endogenous and adoptively transferred immune cells. In this regard, CAFs may be another cell population to be targeted to overcome resistance to not only ICIs but also adoptive cell therapies.
Thus, modulating tumor microenvironment (TME) by targeting immune suppressor cells could be a potential strategy to enhance the efficacy of cancer immunotherapies. However, it remains unclear how these cells contribute to tumor evasion and resistance to immunotherapies including ICIs and engineered T cell therapy.
The aim of this Research Topic is to provide a better understanding of the suppressive mechanism of immune cells and other cells in TME contributing to the immunotherapy resistance, and find the cue for developing novel immunotherapies. We welcome Original Research and Review articles related to, but not limited to following three main axes:
- Immunosuppressive mechanisms mediated by Tregs, MDSCs, TAMs, and CAFs in terms of signaling, metabolism, etc.
- Contribution of these cells to the resistance to ICIs and adoptive cell therapies such as engineered T cell therapies.
- Novel strategies to modulate the TME by direct or indirect targeting of immune suppressor cells.
Several mechanisms of resistance to ICIs are proposed; lack of suitable neo-antigens, impaired presentation of tumor antigens, metabolic/inflammatory mediators, immune suppressor cells, inhibitory signals via alternate immune checkpoints, and severe T cell exhaustion. Regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) are major immune suppressor cells which inhibit antitumor immune responses. Both high infiltration of Tregs in tumor tissues and high frequency of circulating MDSCs are associated with poor responses to ICI treatment, suggesting these immunosuppressive cells may play a key role in resistance to ICI therapy as well as a predictive response marker. Cancer-associated fibroblasts (CAFs) can represent a complex barrier to entry and activity of endogenous and adoptively transferred immune cells. In this regard, CAFs may be another cell population to be targeted to overcome resistance to not only ICIs but also adoptive cell therapies.
Thus, modulating tumor microenvironment (TME) by targeting immune suppressor cells could be a potential strategy to enhance the efficacy of cancer immunotherapies. However, it remains unclear how these cells contribute to tumor evasion and resistance to immunotherapies including ICIs and engineered T cell therapy.
The aim of this Research Topic is to provide a better understanding of the suppressive mechanism of immune cells and other cells in TME contributing to the immunotherapy resistance, and find the cue for developing novel immunotherapies. We welcome Original Research and Review articles related to, but not limited to following three main axes:
- Immunosuppressive mechanisms mediated by Tregs, MDSCs, TAMs, and CAFs in terms of signaling, metabolism, etc.
- Contribution of these cells to the resistance to ICIs and adoptive cell therapies such as engineered T cell therapies.
- Novel strategies to modulate the TME by direct or indirect targeting of immune suppressor cells.
Keywords: tumor microenvironment, immunotherapy, resistance, signaling, tumor evasion
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