Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.

Highlights d CD8 + T cell infiltration in tumors is associated with CCL5 and CXCL9 coexpression d CCL5 is expressed in tumor cells and CXCL9 is induced in APCs in response to IFN-g d CCL5 hi CXCL9 hi tumors are immunoreactive and respond to checkpoint blockade d Cancer cells negatively regulate CCL5 expression by epigenetic silencing mechanisms

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