Modulation of T-cell Function and Survival by the Tumor Microenvironment

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Background

T cells are an essential component of the adaptive immune response, and are characterized by their cell surface T-cell receptors (TCRs). TCRs play a crucial role in the homeostasis of T-cell function. They recognize and bind to antigen peptides on the surface of antigen presenting cells (APCs), which subsequently results in one of many potential actions. These include stimulation of T cell proliferation or survival, pathogenic peptide removal, or tolerance of self-antigens. The various outcomes of TCR activity are due to the heterogeneity of the receptors themselves, their affinity for different antigens, and the accompanying regulatory signals transmitted via diverse accessory receptors that operate in conjunction with the TCR. TCRs and accessory receptors on T lymphocytes act through several different signaling pathways within the T cell, which includes but is not limited to the Ca2+/calcineurin, MAPK, and NF-κB pathways. There are tight regulatory mechanisms of TCR signaling to ensure the correct T cell response to both self and foreign antigens. However, aberrant T cell function can occur during several diseases, including cancer.

During cancer, T cells can become inefficient in removing malignant cells, with dysfunction arising from suboptimal activation of naïve T cells, exhaustion in the context of chronic antigenic stimulation, or factors that decrease T cell survival. Studies around this subject have identified that the tumor microenvironment is partly responsible for this altered behavior from T cells. There are tumor- or immune cell-derived microenvironmental factors, including chemokines, cytokines, and metabolites that can affect T cells.

The aim of this research topic is to collect articles delineating the signaling events that contribute to altered T cell function in cancer. By understanding how the components of the tumor microenvironment impact TCRs, either in a direct or indirect fashion mediated by accessory receptors, progress can be made in designing effective therapeutic strategies against aberrant T cell function.

This research topic welcomes articles of all types on different constituents of the tumor microenvironment (e.g. cytokines, chemokines, or metabolites) and their effect on TCR/accessory receptor signaling and/or T cell function and survival.

Keywords: T cell, tumor microenvironment, t cell receptor

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.

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