Zhang Jing, Li Albert M, Kansler Emily R, Li Ming O
Immunology Program, Memorial Sloan Kettering Cancer Center, New York City, New York, USA.
Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York City, New York, USA.
Immunol Rev. 2024 May;323(1):150-163. doi: 10.1111/imr.13319. Epub 2024 Mar 20.
Cancer progression can be restrained by tumor-infiltrating lymphocytes in a process termed cancer immunosurveillance. Based on how lymphocytes are activated and recruited to the tumor tissue, cancer immunity is either pre-wired, in which innate lymphocytes and innate-like T cells are directly recruited to and activated in tumors following their differentiation in primary lymphoid organs; or priming-dependent, in which conventional adaptive T cells are first primed by cognate antigens in secondary lymphoid organs before homing to and reactivated in tumors. While priming-dependent cancer immunity has been a focus of cancer immunology research for decades, in part due to historical preconception of cancer theory and tumor model choice as well as clinical success of conventional adaptive T cell-directed therapeutic programs, recent studies have revealed that pre-wired cancer immunity mediated by tissue-resident type 1 innate lymphoid cells (ILC1s) and killer innate-like T cells (ILTCKs) is an integral component of the cancer immunosurveillance process. Herein we review the distinct ontogenies and cancer-sensing mechanisms of ILC1s and ILTCKs in murine genetic cancer models as well as the conspicuously conserved responses in human malignancies. How ILC1s and ILTCKs may be targeted to broaden the scope of cancer immunotherapy beyond conventional adaptive T cells is also discussed.
癌症进展可被肿瘤浸润淋巴细胞在一个称为癌症免疫监视的过程中所抑制。根据淋巴细胞如何被激活并募集到肿瘤组织,癌症免疫分为预编程型,即先天淋巴细胞和类先天T细胞在初级淋巴器官分化后直接被募集到肿瘤并在其中被激活;或依赖启动型,即传统适应性T细胞首先在次级淋巴器官中被同源抗原启动,然后归巢到肿瘤并在其中重新激活。虽然依赖启动型癌症免疫几十年来一直是癌症免疫学研究的重点,部分原因是癌症理论和肿瘤模型选择的历史先入之见以及传统适应性T细胞导向治疗方案的临床成功,但最近的研究表明,由组织驻留1型先天淋巴细胞(ILC1s)和杀伤性类先天T细胞(ILTCKs)介导的预编程癌症免疫是癌症免疫监视过程的一个组成部分。在此,我们综述了小鼠遗传癌症模型中ILC1s和ILTCKs不同的个体发生和癌症感知机制,以及人类恶性肿瘤中明显保守的反应。我们还讨论了如何靶向ILC1s和ILTCKs以扩大癌症免疫治疗的范围,使其超越传统适应性T细胞。