The tumor-promoting effects of the adaptive immune system: a cause of hyperprogressive disease in cancer?
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Cellular and Molecular Life Sciences
REVIEW
The tumor‑promoting effects of the adaptive immune system: a cause of hyperprogressive disease in cancer? Fabrizio Marcucci1 · Cristiano Rumio1 Received: 27 April 2020 / Revised: 1 July 2020 / Accepted: 20 July 2020 © Springer Nature Switzerland AG 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. Keywords Tumor promoting · Immune response · T cells · B cells · Antibodies · Hyperprogressive disease
Introduction Tumors express molecules that are recognized as foreign by the immune system, i.e., tumors are antigenic. As in most other cases where the immune system is faced with antigens, also antigenic tumor cells set in motion two main branches of the immune system, the innate and the adaptive immune system. The innate immune system rests on the recognition of molecules referred to as damage-associated molecular patterns by pattern recognition receptors [1]. Such recognition leads to the release of inflammatory mediators and activation of innate immune cell populations, including cytotoxic populations, which act as a first line of defense against tumor progression [2]. Moreover, the innate immune system is involved in the onset and promotion of adaptive antitumor immune responses which rest on the specific recognition of tumor antigens and the activation of two classes of effector responses: antibody-based, humoral immune responses and * Fabrizio Marcucci [email protected] 1
Department of Pharmacological and Biomolecular Sciences, University of Milan, via Trentacoste 2, Milan, Italy
cell-mediated immune responses which rely on the focused release of cytokines and the cytotoxic effects of antigenspecific T-lymphocytes (cytotoxic T lymphocyte, CTL) [2]. Adaptive immune responses are recognized to play
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