Immunogenic Cell Death and Elimination of Immunosuppressive Cells: A Double-Edged Sword of Chemotherapy

Abstract

Chemotherapy is initially used to kill proliferative cells. In the current area of emerging immunotherapy, chemotherapies have shown their ability to modulate the tumor micro environment and immune response. We focus here on two main effects: first, immunogenic cell death, defined as a form of regulated cell death (RCD) that is sufficient to activate an adaptive immune response in immunocompetent hosts; and second, the depletion of suppressive cells, known to play a major role in immune escape and resistance to immunotherapy. In this review, we present a review of different classically used chemotherapies focusing on this double effect on immunity. These immunological effects of chemotherapy could be exploited to promote efficacy of immunotherapy. Broadening our understanding will make it possible to provide rationales for the combination of chemoimmunotherapy in early clinical trials.

Calreticulin—Multifunctional Chaperone in Immunogenic Cell Death: Potential Significance as a Prognostic Biomarker in Ovarian Cancer Patients

“…In contrast, oxaliplatin, a third-generation platinum analogue, seems to be indisputable type I ICD inducer. On the other hand, physical methods, such as photodynamic therapy, high hydrostatic pressure or molecules as oncolytic viruses are the example of type II inducers [ 30 , 35 , 36 , 37 ]. Both types of inducers, by the combined action of ER stress and ROS generation which activates danger signaling pathways, are able to trigger the timely release or membrane exposure of a series of DAMPs.…”

“…Among DAMPs most frequently associated with ICD are CRT, adenosine-5′-triphosphate (ATP), non-histone chromatin-binding protein—high-mobility group box 1 (HMGB1), type I and II interferons (IFN), annexin A1 and heat shock proteins (HSPs) 70 and 90. The majority of these molecules have non-immunogenic functions inside cell, but when exposed on cell surface or released extracellularly they become immunogenic [ 22 , 35 , 36 ].…”

“…The studies assessing the ability of drugs or physical factors to induce ICD are based on: (1) detection of DAMPs, primarily ecto-CRT, extracellular release of ATP and HMGB1, as well as extracellular expression of HSP70 and HSP90; (2) determination of immunological parameters strongly connected with ICD, i.e., expression of CD91 and CD14 molecules or TLR4 on the surface of APCs; (3) stimulation of type I IFN responses [ 34 , 36 , 43 ]. Since, this paper is dedicated to calreticulin only, below we have presented the review of available data on the capacity of anti-ovarian cancer drugs to the induction of ecto-CRT on ovarian cancer cells.…”

Editorial: Immune Regulation in Kidney Diseases: Importance, Mechanism and Translation

“…Opportunistic infections such as fungal is not rare in kidney transplant patients. In this case, Fumet et al reported a patient with pulmonary mucormycosis 38 days after kidney transplantation ( 1 ). This case is a reminder that early diagnosis of fungal infection is imperative.…”

Dendritic Cells: Behind the Scenes of T-Cell Infiltration into the Tumor Microenvironment

“…Many chemotherapeutic agents are known to promote antitumor activity by triggering immunogenic cell death (ICD) of tumor cells [ 103 , 104 ]. ICD begins with the induction of cellular stress and culminates in cell death following exposure to and release of several DAMPs.…”