The Relationship Between Immunogenic Cell Death and Cellular Senescence in Cancer Immunotherapy

Despite rapid advances in anticancer therapy, cancer incidence and mortality remain substantial worldwide. Although immune checkpoint inhibitors (ICIs), including anti-PD-1/PD-L1 and anti-CTLA-4 therapies, have transformed cancer treatment by harnessing host antitumor immunity, their efficacy remains limited to a subset of patients, largely because of the complexity of the tumor microenvironment. This review examines drug-induced immunogenic cell death (ICD) and drug-induced senescence as complementary strategies for overcoming these limitations and enhancing immunotherapeutic responses. We further highlight evidence that agents capable of inducing ICD may instead promote cellular senescence when administered at lower concentrations for prolonged periods, indicating that these distinct cellular outcomes can be determined by drug dose and treatment duration. This dose- and time-dependent relationship suggests that the therapeutic application of the same agent may require optimization according to the patient’s condition and tumor stage. Collectively, this review provides an integrated perspective on the selective use of ICD and senescence induction to enhance antitumor immunity, improve therapeutic outcomes, and potentiate synergistic responses to existing ICIs.