Dataset Information

Intratumoral PD-1⁺CD8⁺ T cells associate poor clinical outcomes and adjuvant chemotherapeutic benefit in gastric cancer.

ABSTRACT:

Background

Although PD-1 has been reported to be a marker of T-cell exhaustion in several malignancies, the biological role of PD-1⁺CD8⁺ T cells in gastric cancer (GC) remains unclear. Herein, we aimed to investigate the role of PD-1⁺CD8⁺ T cells in the tumour microenvironment and its clinical significance in GC.

Designs

This study included 441 tumour microarray specimens and 60 Flow cytometry specimens of GC patients from Zhongshan Hospital, and 250 GC patients from the Asian Cancer Research Group.

Results

Here, we demonstrated that PD-1⁺CD8⁺ T cells functioned as an independent adverse prognosticator in GC. In addition, an abundance of intratumoral PD-1⁺CD8⁺ T cells indicated worse chemotherapeutic responsiveness to fluorouracil in Stage III GC patients. Mechanistically, PD-1⁺CD8⁺ T cell high infiltration indicated an exhausted phenotype of global CD8⁺ T cells in GC tissues, which was characterised by elevated immune checkpoint expression including CTLA-4 and TIM-3, whereas decreased expression of perforin. Furthermore, PD-1⁺CD8⁺ T cell high-infiltration patients with Stage III GC held elevated activity of several therapeutic signal pathways.

Conclusions

Our study highlighted that PD-1⁺CD8⁺ T cell abundance predicts inferior prognosis in GC, and may serve as a novel predictive biomarker to guide therapeutic option.

SUBMITTER: Yu K

PROVIDER: S-EPMC9596411 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Intratumoral PD-1<sup>+</sup>CD8<sup>+</sup> T cells associate poor clinical outcomes and adjuvant chemotherapeutic benefit in gastric cancer.

Yu Kuan K Gu Yun Y Zhang Puran P Fang Hanji H Cao Yifan Y Wang Jieti J Lin Chao C Liu Hao H Zhang Heng H He Hongyong H Li Ruochen R Qin Jing J Li He H Xu Jiejie J

British journal of cancer 20220824 9

<h4>Background</h4>Although PD-1 has been reported to be a marker of T-cell exhaustion in several malignancies, the biological role of PD-1<sup>+</sup>CD8<sup>+</sup> T cells in gastric cancer (GC) remains unclear. Herein, we aimed to investigate the role of PD-1<sup>+</sup>CD8<sup>+</sup> T cells in the tumour microenvironment and its clinical significance in GC.<h4>Designs</h4>This study included 441 tumour microarray specimens and 60 Flow cytometry specimens of GC patients from Zhongshan Hosp ...[more]

PMID: 36002752

Similar Datasets

Project description:BackgroundPrevious studies have shown that PD-L1-positive advanced gastric cancer (GC) patients could achieve clinical benefit after receiving immune checkpoint inhibitors (ICI) in initial or subsequent therapy. A number of prospective studies such as Keynote-158 have demonstrated that PD-L1-negative patients who tested as microsatellite instability-high (MSI-H) or tumor mutational burden-high (TMB-H) can benefit from ICIs. In the search for more biomarker for immunotherapy, some studies showed that patients with a specific characteristic to tumor microenvironment (TME) were associated with better prognosis. This study aimed to explore the association between the TME and immunotherapy in PD-L1 negative GC patients.MethodsThis study was a retrospective cohort study. Twenty-six CPS PD-L1 negative stage IV advanced GC patients treated with chemoimmunotherapy in Shenzhen Hospital of Peking University were retrospectively enrolled according to the inclusion criteria. Their clinical characteristics were assessed and recorded by independent clinicians. Follow-up data was conducted through the Internet or visit. Respond to treatment was evaluated by RECIST 1.1. The primary outcome was progression-free survival (PFS). The level of tumor-infiltrating lymphocytes (TILs) was measured by multiplex immunofluorescence (mIF) among these patients. Cox proportional hazards analysis was performed to analyzed the correlation between PFS and clinical characteristics including TILs.ResultsAmong 26 patients, 5 patients (19.2%) were on complete response (CR) and 9 patients (34.6%) were in partial response (PR), while 7 patients (26.9%) experienced stable disease (SD). Intratumoral CD8+ T cells were obviously increased in CPS PD-L1 negative patients who responded to chemoimmunotherapy, compared with patients who did not respond (P=0.011). And higher level of CD8+ TILs was demonstrated to associate with better PFS in CPS PD-L1-negative patients treated with chemoimmunotherapy (HR =23.70, 95% CI: 1.15-488.30, P=0.04).ConclusionsIntratumoral CD8+ TILs may be a potential positive predictive factor of clinical response for chemoimmunotherapy in PD-L1-negative advanced GC. However, the results need to be further confirmed in a cohort with more subjects due to a limited sample sizes in present study.

Dataset Information

Intratumoral PD-1⁺CD8⁺ T cells associate poor clinical outcomes and adjuvant chemotherapeutic benefit in gastric cancer.

Background

Designs

Results

Conclusions

Publications

Intratumoral PD-1<sup>+</sup>CD8<sup>+</sup> T cells associate poor clinical outcomes and adjuvant chemotherapeutic benefit in gastric cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Intratumoral PD-1+CD8+ T cells associate poor clinical outcomes and adjuvant chemotherapeutic benefit in gastric cancer.

Background

Designs

Results

Conclusions

Publications

Intratumoral PD-1<sup>+</sup>CD8<sup>+</sup> T cells associate poor clinical outcomes and adjuvant chemotherapeutic benefit in gastric cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Intratumoral PD-1⁺CD8⁺ T cells associate poor clinical outcomes and adjuvant chemotherapeutic benefit in gastric cancer.