About this Research Topic
DNA mismatch repair deficiency (MMRd) cancers have exceptional response rates to immune checkpoint blockade (ICB) (~50%). This recognition resulted in FDA approval for the tissue-agnostic deployment of checkpoint inhibitors in MMRd cancers. This favorable MMRd tumor response to ICB is probably due to high immune infiltration in the tumor microenvironment (TME), likely driven by multiple mechanisms, including a high neoantigen load and the activation of the cGAS-cGAMP-STING pathway. In accordance with the hypothesis that favorable MMRd tumor response to ICB is probably due to high tumor mutational burden (TMB) and the consequent high immune infiltration in the TME, ICB has also demonstrated significant clinical benefit in other inflamed/TMB-high tumors, such as melanoma and lung tumors.
However, most patients with cancer fail to respond to ICB treatment, suggesting that resistance mechanisms are likely affecting immune surveillance and the success of therapy. Therefore, it is critical to investigate the specific immune resistance mechanisms that develop in these patients during tumor evolution and following ICB failure. There is more and more evidence suggesting that myeloid cells, especially macrophages and monocytes, are involved in the response and resistance to ICB. Thus, better characterization of their role will help to develop therapies that are more suitable.
The aim of this Research Topic is to understand the role of myeloid cells, especially macrophages and monocytes, in the response and resistance to immune checkpoint blockade in tumors with high tumor mutational burden. The goal is to characterize the resistance mechanisms to immunotherapies driven by myeloid cells. New immunotherapies involving myeloid targeting strategies or combination therapies involving T cell and myeloid cells may help to overcome this resistance. The characterization of myeloid subsets in tumors with resistance to immunotherapy may be investigated using patient cohort, in vivo murine models or 3D in vitro tumor models to study myeloid/T cell interactions following ICB.
This Research Topic accepts Original Research, Systematic Review, Methods, Review and Mini-Review, Clinical Trial, Technology and Code, Perspective, and Case Report. We welcome manuscripts focusing on, but not limited to, the following sub-topics:
• Resistance mechanisms to immunotherapies driven by myeloid cells
• New immunotherapies involving myeloid targeting strategies
• Combination therapies involving T cell and myeloid cells
• Characterization of myeloid subsets in tumors with resistance to immunotherapy
• 3D in vitro tumor models to study myeloid/T cell interactions following ICB.
However, most patients with cancer fail to respond to ICB treatment, suggesting that resistance mechanisms are likely affecting immune surveillance and the success of therapy. Therefore, it is critical to investigate the specific immune resistance mechanisms that develop in these patients during tumor evolution and following ICB failure. There is more and more evidence suggesting that myeloid cells, especially macrophages and monocytes, are involved in the response and resistance to ICB. Thus, better characterization of their role will help to develop therapies that are more suitable.
The aim of this Research Topic is to understand the role of myeloid cells, especially macrophages and monocytes, in the response and resistance to immune checkpoint blockade in tumors with high tumor mutational burden. The goal is to characterize the resistance mechanisms to immunotherapies driven by myeloid cells. New immunotherapies involving myeloid targeting strategies or combination therapies involving T cell and myeloid cells may help to overcome this resistance. The characterization of myeloid subsets in tumors with resistance to immunotherapy may be investigated using patient cohort, in vivo murine models or 3D in vitro tumor models to study myeloid/T cell interactions following ICB.
This Research Topic accepts Original Research, Systematic Review, Methods, Review and Mini-Review, Clinical Trial, Technology and Code, Perspective, and Case Report. We welcome manuscripts focusing on, but not limited to, the following sub-topics:
• Resistance mechanisms to immunotherapies driven by myeloid cells
• New immunotherapies involving myeloid targeting strategies
• Combination therapies involving T cell and myeloid cells
• Characterization of myeloid subsets in tumors with resistance to immunotherapy
• 3D in vitro tumor models to study myeloid/T cell interactions following ICB.
Keywords: Macrophages, monocytes, resistance, immunotherapy, PD1, CTLA4
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.
