The tumor-promoting effects of the adaptive immune system: a cause of hyperprogressive disease in cancer?

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.