Crosstalk Between Innate and Adaptive Immunity in Colorectal Cancer: Implications for Immunotherapy

The evolution of many solid tumors including colorectal cancer (CRC) is influenced by complex interactions between tumor cells and immune cells of the local microenvironment, especially tumor infiltrating lymphocytes (TILs), depending on many different intrinsic factors including tissue specific factors and genetic abnormalities of the tumor. These interactions lead to the development of a local immune response that can have immunosuppressive or immunostimulatory properties.

Cancer immunotherapy aiming at restoring or boosting the adaptive immune response has led to successful clinical trials in some solid tumors including malignant melanoma, non-small cell lung cancer or head and neck cancer. However, in CRC, the efficacy of immunotherapies, mainly based on monoclonal antibodies targeting inhibitory receptors on T cells (so-called immune checkpoint blockade) is limited, being successful only in a subset of metastatic CRC (mCRC) with microsatellite instability (MSI) and high mutational load, but overall unsuccessful in microsatellite stable (MSS) CRC, which constitute the vast majority of CRC. Response to immune checkpoint blockade therapy generally correlates with mutational load among most solid cancer types, while the the lack of response in MSS CRC is not reflected by low mutation rates, indicating yet unidentified mechanisms of immune evasion in these tumors.

Combining therapeutic strategies that can inhibit immunosuppression while activating tumor-specific T lymphocytes able to kill tumor cells currently represents the most promising therapeutic approach in CRC. In addition, since many innate immune cells are present within the tumor and since signaling pathways such as the inflammasome can modulate the adaptive immune response, a deeper understanding of the complex interplay between the innate and adaptive arm of the immune system is necessary in CRC and should lead to new therapeutic options.

In this Research Topic, we aim to provide current advances on the interactions between tumor cells and immune cells including the complex crosstalk between innate and adaptive immunity in triggering an anti-tumor response. We welcome submissions of Original Research articles in human CRC and preclinical models, Reviews, Clinical Trials and Perspectives focusing on the following subtopics :

- Comprehensive understanding of the anti-tumor immune response in CRC (immune cell subsets etc)
- Mechanisms of immune evasion in CRC (immune desertification, suppression of immunogenicity or immune cell activation etc)
- Emerging biomarkers for immunotherapy in CRC (immune checkpoints and also innate arm of immunity ; tumor mutation burden and neoantigens)
- Modulation of the anti-tumor immune response by innate immune cells and innate immunity pathways including the inflammasome, as well as by the microbiome
- Immunomodulatory functions of tumor cells and how tumor cells can impact the immune response in CRC (cytokines, signaling pathways…)
- Therapeutic approaches targeting agents and/or signaling pathways bridging innate and adaptive immunity

Note: Submissions consisting solely of bioinformatic investigation of publicly available genomic / transcriptomic data are not in scope for this Research Topic.