ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicTargeting Immune Suppression in Gastrointestinal Cancers: Unveiling Mechanisms and Therapeutic PotentialView all articles
Intra-tumoral NK cells and their Association with Patient Outcomes: A novel Prognostic model Incorporating NK Cells and Clinicopathologic features in Gastric Cancer
Provisionally accepted
Masanori Oshi1*
Yuko Tamura1Rongrong Wu2Colin J. Rog3
Li Yan3Kizuki Yuza1Takashi Kosaka1Hirotoshi Akiyama1Takashi Ishikawa2
Kazuaki Takabe3Itaru Endo1- 1Yokohama City University Hospital, Yokohama, Japan
- 2Tokyo Ika Daigaku, Shinjuku, Japan
- 3Roswell Park Comprehensive Cancer Center, Buffalo, United States
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Background: Natural killer (NK) cell infiltration has been implicated in the prognosis of gastric cancer patients. However, NK cell infiltration fraction has not yet been used routinely in clinical practice due to a lack of a measure for accurate quantification. Methods: NK cell infiltration fraction was quantified using a deconvolution tool and its clinical relevance was investigated in gastric cancer patients from our institution (Yokohama City University Hospital (YCU) and those present in publicly available cohorts with transcriptome data (TCGA, GSE84437 and GSE167036). Results: In the single cell sequencing cohort, the distribution of NK cells was similar to that of NK cell-related gene expression. High NK cell infiltration in gastric cancer correlated with enriched immune gene sets, such as IFN-α and IFN-γ responses, and also linked to increased cytolytic activity and low stromal cell infiltration along with higher mutation rates. Clinically, high NK cell infiltration was associated with better overall survival and improved response to neoadjuvant chemotherapy. Additionally, combining NK cell score with clinicopathological factors, including age at a diagnosis and AJCC T-and N-category, provided a powerful prognostic score for gastric cancer patients which was found to be consistent in multiple cohorts. Conclusions: Gastric cancer with high NK cell infiltration is associated with increased immune activity and lower stromal cell infiltration, potentially impacting patient prognosis. Combining clinicopathological factors with NK cell score provides a powerful tool for prognostication of gastric cancer patients.
Keywords: gastric cancer, NK cells, prognostic biomarker, Survival, tumor micro environment (TME)
Received: 04 Dec 2025; Accepted: 18 Dec 2025.
Copyright: © 2025 Oshi, Tamura, Wu, Rog, Yan, Yuza, Kosaka, Akiyama, Ishikawa, Takabe and Endo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Masanori Oshi
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