Immunogenic cell death (ICD) refers to an immunologically distinct process of regulated cell death that activates, rather than suppresses, innate and adaptive immune responses. Such responses culminate into T cell-driven immunity against antigens derived from dying cancer cells. The potency of ICD is dependent on the immunogenicity of dying cells as defined by the antigenicity of these cells and their ability to expose immunostimulatory molecules like damage-associated molecular patterns (DAMPs) and cytokines like type I interferons (IFNs). Moreover, it is crucial that the host's immune system can adequately detect the antigenicity and adjuvanticity of these dying cells. Over the years, several well-known chemotherapies have been validated as potent ICD inducers, including (but not limited to) anthracyclines, paclitaxels, and oxaliplatin. Such ICD-inducing chemotherapeutic drugs can serve as important combinatorial partners for anti-cancer immunotherapies against highly immuno-resistant tumors. In this Trial Watch, we describe current trends in the preclinical and clinical integration of ICD-inducing chemotherapy in the existing immuno-oncological paradigms.

• Keywords
• CAR T cells, antigen-presenting cells, chemotherapy, danger signals, dendritic cell, immune-checkpoint blockers, immunogenic cell death, immunotherapy,
• MeSH
• Cell Death MeSH
• Cytokines metabolism   MeSH
• Immunogenic Cell Death MeSH
• Humans MeSH
• Neoplasms * MeSH
• Antineoplastic Agents * pharmacology   therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Cytokines MeSH
• Antineoplastic Agents * MeSH

The immune checkpoint inhibitors have revolutionized cancer immunotherapy. These inhibitors are game changers in many cancers and for many patients, sometimes show unprecedented therapeutic efficacy. However, their therapeutic efficacy is largely limited in many solid tumors where the tumor-controlled immune microenvironment prevents the immune system from efficiently reaching, recognizing, and eliminating cancer cells. The tumor immune microenvironment is largely orchestrated by immune cells through which tumors gain resistance against the immune system. Among these cells are mast cells and dendritic cells. Both cell types possess enormous capabilities to shape the immune microenvironment. These capabilities stage these cells as cellular checkpoints in the immune microenvironment. Regaining control over these cells in the tumor microenvironment can open new avenues for breaking the resistance of solid tumors to immunotherapy. In this review, we will discuss mast cells and dendritic cells in the context of solid tumors and how these immune cells can, alone or in cooperation, modulate the solid tumor resistance to the immune system. We will also discuss how this modulation could be used in novel immunotherapeutic modalities to weaken the solid tumor resistance to the immune system. This weakening could then help other immunotherapeutic modalities engage against these tumors more efficiently.

• Keywords
• cellular checkpoint, dendritic cells, immunotherapy, mast cells,
• MeSH
• Dendritic Cells pathology   MeSH
• Immunotherapy MeSH
• Immune Checkpoint Inhibitors MeSH
• Humans MeSH
• Mast Cells * pathology   MeSH
• Tumor Microenvironment MeSH
• Neoplasms * pathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Immune Checkpoint Inhibitors MeSH