NK細胞とキラーT細胞の協調免疫機構の解明に成功 －難治性腫瘍のための次世代のがんワクチンや免疫療法の設計に貢献－

2026-08-04 理化学研究所

腫瘍組織におけるNK-CTLの協調

＜関連情報＞

• https://www.riken.jp/press/2026/20260804_1/index.html
• https://aacrjournals.org/cancerres/article-abstract/doi/10.1158/0008-5472.CAN-25-4957/787203/Multiomics-Dissection-Reveals-Natural-Killer-Cell

マルチオミクス解析により、ナチュラルキラー細胞とCD8 + T細胞の協調作用が免疫刺激性腫瘍微小環境の形成に関与 していることが明らかになった Multiomics Dissection Reveals Natural Killer Cell–CD8+ T-cell Cooperation in Shaping an Immunostimulatory Tumor Microenvironment

Kanako Shimizu;An Sanpei;Yan Liu;Takuya Ishibashi;Marin Yanagawa;Hiroshi Nakazato;Jun Shinga;Shogo Ueda;Satoru Yamasaki;Shin-ichiro Fujii
Cancer Research  Published: August 03 2026
DOI:https://doi.org/10.1158/0008-5472.CAN-25-4957

Abstract

Immune evasion remains a major barrier to effective immunotherapy in cancer. Coordinated activation of different immune cell types shapes immune responses within the tumor microenvironment (TME). In this study, we uncovered a spatiotemporal synergy between cytotoxic T lymphocytes (CTL) and natural killer (NK) cells in tumors with low T-cell infiltration. An integrative multiomics approach combining spatial transcriptomics, single-cell RNA sequencing, and high-dimensional flow cytometry demonstrated that vaccination, capable of activating both innate and adaptive immunity, rapidly reshapes the TME. Early infiltration of IRF8⁺KLRG1⁺ NK cells established a chemokine-rich niche together with myeloid cells that promoted the recruitment of antigen-primed CXCR3⁺ CTLs. The accompanying inflammatory monocyte recruitment and dendritic cell activation led to the coordinated structural and chemotactic remodeling of the TME. Functionally, NK–CTL clustering at the tumor margin was associated with enhanced cytotoxic activity and sustained immune engagement. These spatially organized immune interactions involved CCR5–CCL5 and CXCR3–CXCL9 signaling pathways that coordinate communication between innate and adaptive immune compartments. Together, these findings reveal a previously unrecognized NK–CTL cooperative program that promotes the transition of poorly infiltrated tumors toward an inflamed, immune-responsive state. More broadly, this study illustrates how spatially resolved multiomics approaches can uncover immune interactions and provides a conceptual framework for designing next-generation immunotherapies that mobilize coordinated innate and adaptive immunity.