Trial Watch: Immunogenic cell death inducers for anticancer chemotherapy

Abstract

The term "immunogenic cell death" (ICD) is now employed to indicate a functionally peculiar form of apoptosis that is sufficient for immunocompetent hosts to mount an adaptive immune response against dead cell-associated antigens. Several drugs have been ascribed with the ability to provoke ICD when employed as standalone therapeutic interventions. These include various chemotherapeutics routinely employed in the clinic (e.g., doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin) as well as some anticancer agents that are still under preclinical or clinical development (e.g., some microtubular inhibitors of the epothilone family). In addition, a few drugs are able to convert otherwise non-immunogenic instances of cell death into bona fide ICD, and may therefore be employed as chemotherapeutic adjuvants within combinatorial regimens. This is the case of cardiac glycosides, like digoxin and digitoxin, and zoledronic acid. Here, we discuss recent developments on anticancer chemotherapy based on ICD inducers.

Keywords: ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CML, chronic myeloid leukemia; DAMP, damage-associated molecular pattern; EGFR, epidermal growth factor receptor; EOX, epirubicin plus oxaliplatin plus capecitabine; ER, endoplasmic reticulum; FDA, Food and Drug Administration; FOLFIRINOX, folinic acid plus 5-fluorouracil plus irinotecan plus oxaliplatin; FOLFOX, folinic acid plus 5-fluorouracil plus oxaliplatin; GEMOX, gemcitabine plus oxaliplatin; GM-CSF, granulocyte-macrophage colony-stimulating factor; HCC, hepatocellular carcinoma; ICD, immunogenic cell death; MM, multiple myeloma; NHL, non-Hodgkin's lymphoma; NSCLC, non-small cell lung carcinoma; TACE, transcatheter arterial chemoembolization; XELOX, capecitabine plus oxaliplatin; antigen-presenting cell; autophagy; damage-associated molecular pattern; dendritic cell; endoplasmic reticulum stress; mAb, monoclonal antibody; type I interferon.