Intratumoral CD8+ T cells as a potential positive predictor of chemoimmunotherapy response in PD-L1-negative advanced gastric cancer patients: a retrospective cohort study

Gangling Tong; Meiqin Zhu; Yaoxu Chen; Shubo Wang; Boran Cheng; Shubin Wang; Wangjun Liao

doi:10.21037/jgo-22-644

Intratumoral CD8⁺ T cells as a potential positive predictor of chemoimmunotherapy response in PD-L1-negative advanced gastric cancer patients: a retrospective cohort study

J Gastrointest Oncol. 2022 Aug;13(4):1668-1678. doi: 10.21037/jgo-22-644.

Authors

Gangling Tong^#^{1

2}, Meiqin Zhu^#³, Yaoxu Chen^#⁴, Shubo Wang⁴, Boran Cheng², Shubin Wang², Wangjun Liao¹

Affiliations

¹ Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
² Department of Oncology, Peking University Shenzhen Hospital, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute of Shenzhen-Peking University-Hong Kong University of Science and Technology (PKU-HKUST) Medical Center, Shenzhen, China.
³ Department of Medical Oncology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China.
⁴ The Medical Department, 3D Medicines Inc., Shanghai, China.

^# Contributed equally.

Abstract

Background: Previous 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.

Methods: This 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.

Results: Among 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).

Conclusions: Intratumoral 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.

Keywords: CD8+ T cells; Gastric cancer; PD-L1; chemoimmunotherapy; immune microenvironment.