The tumor-promoting effects of the adaptive immune system: a cause of hyperprogressive disease in cancer?
Cellular and molecular life sciences : CMLS(2020)
Abstract
Adaptive antitumor immune responses, either cellular or humoral, aim at eliminating tumor cells expressing the cognate antigens. There are some instances, however, where these same immune responses have tumor-promoting effects. These effects can lead to the expansion of antigen-negative tumor cells, tumor cell proliferation and tumor growth, metastatic dissemination, resistance to antitumor therapy and apoptotic stimuli, acquisition of tumor-initiating potential and activation of various forms of survival mechanisms. We describe the basic mechanisms that underlie tumor-promoting adaptive immune responses and try to identify the variables that induce the switching of a tumor-inhibitory, cellular or humoral immune response, into a tumor-promoting one. We suggest that tumor-promoting adaptive immune responses may be at the origin of at least a fraction of hyperprogressive diseases (HPD) that are observed in cancer patients during therapy with immune checkpoint inhibitors (ICI) and, less frequently, with single-agent chemotherapy. We also propose the use of non-invasive biomarkers allowing to predict which patients may undergo HPD during ICI and other forms of antitumor therapy. Eventually, we suggest possibilities of therapeutic intervention allowing to inhibit tumor-promoting adaptive immune responses.
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