细胞毒性抗癌疗法在潜在的压力和炎症信号传导的背景下激活程序性细胞死亡，从而引发危险信号、细胞因子和趋化因子的发射。这些免疫调节分泌组以协调一致的方式刺激抗原呈递和 T 细胞介导的抗癌免疫反应。在某些情况下，与细胞死亡相关的分泌组会吸引免疫抑制细胞以促进肿瘤进展。就目前而言，癌细胞死亡引起的肿瘤微环境变化有助于抗肿瘤或促肿瘤作用仍然很大程度上未知。这很难检查，因为细胞死亡经常被肿瘤破坏，以规避自然的和治疗诱导的免疫监视。在这里，我们深入探讨了评估细胞死亡对肿瘤消除或癌症进展的贡献的重要但尚未充分研究的方面，包括肿瘤相关遗传学、表观遗传学和致癌因素在破坏免疫原性细胞死亡中的作用。这一观点还将为未来的研究如何解决细胞死亡的复杂抗肿瘤和促肿瘤免疫效应提供见解，同时考虑肿瘤遗传学和潜在微环境的变化。©2023由美国癌症研究协会出版。

Cytotoxic anticancer therapies activate programmed cell death in the context of underlying stress and inflammatory signaling to elicit the emission of danger signals, cytokines, and chemokines. In a concerted manner, these immunomodulatory secretomes stimulate antigen presentation and T cell-mediated anticancer immune responses. In some instances, cell death-associated secretomes attract immunosuppressive cells to promote tumor progression. As it stands, cancer cell death-induced changes in the tumor microenvironment that contribute to antitumor or protumor effects remain largely unknown. This is complicated to examine because cell death is often subverted by tumors to circumvent natural, and therapy-induced, immunosurveillance. Here, we provide insights into important but understudied aspects of assessing the contribution of cell death to tumor elimination or cancer progression, including the role of tumor-associated genetics, epigenetics, and oncogenic factors in subverting immunogenic cell death. This perspective will also provide insights on how future studies may address the complex antitumor and protumor immunologic effects of cell death, while accounting for variations in tumor genetics and underlying microenvironment.©2023 The Authors; Published by the American Association for Cancer Research.