Back to the Future: Spatiotemporal Determinants of NK Cell Antitumor Function

Abstract

NK cells play a crucial role in host protection during tumorigenesis. Throughout tumor development, however, NK cells become progressively dysfunctional through a combination of dynamic tissue-specific and systemic factors. While a number of immunosuppressive mechanisms present within the tumor microenvironment have been characterized, few studies have contextualized the spatiotemporal dynamics of these mechanisms during disease progression and across anatomical sites. Understanding how NK cell immunosuppression evolves in these contexts will be necessary to optimize NK cell therapy for solid and metastatic cancers. Here, we outline the spatiotemporal determinants of antitumor NK cell regulation, including heterogeneous tumor architecture, temporal disease states, diverse cellular communities, as well as the complex changes in NK cell states produced by the sum of these higher-order elements. Understanding of the signals encountered by NK cells across time and space may reveal new therapeutic targets to harness the full potential of NK cell therapy for cancer.

No time to die: Epigenetic regulation of natural killer cell survival

“…[201][202][203][204] This hypothesis was recently supported by in vivo photolabeling and fate-mapping of tumor-infiltrating mouse NK cells, 205 suggesting that TME-induced transcriptional changes occur rapidly following infiltration into solid tumors. While the potential mechanisms underlying NK cell dysfunction in the tumor microenvironment (TME) have been reviewed previously, 206,207 we will briefly focus on studies identifying distinct epigenetic modifications in NK cells that may regulate NK cell survival in the TME. NK cells, in comparison to other immune populations in common human solid tumors, are rare.…”

Effectiveness and safety of COVID-19 vaccines in patients with oncological diseases: State-of-the-art

“…Increased Bregs express immunosuppressive properties in gastric cancer through the secretion of anti-inflammatory molecules, such as IL-10, and facilitating the conversion of T cells to regulatory T cells[ 44 , 51 , 52 ]. Additionally, tumor progression is associated with the dysfunction of natural killer cells due to the combined action of tissue-specific and systemic factors[ 53 ]. All of these immune alterations in cancer patients contribute to the differences in immune response after vaccination, including after COVID-19 vaccine administration.…”

Research progress in leveraging biomaterials for enhancing NK cell immunotherapy

“…协同其他免疫细胞从而间接激活NK细胞是更加普遍高效的策略。NK细胞的活化和抑制涉及多种细胞的相互作用 ［ 58 ］ 。封装TLR7/8激动剂的酸碱度响应性纳米粒在肿瘤部位释放，刺激树突状细胞的活化与成熟，分泌包括IL-12、IL-18、γ干扰素在内的多种细胞因子，从而维持NK细胞持久活化 ［ 59 ］ 。活化的NK细胞能释放CCL5、XCL1和XCL2等，促进树突状细胞招募，从而协调先天免疫和适应性免疫在抗肿瘤中的作用 ［ 60 - 61 ］ 。…”