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. 2025 Aug 13.
doi: 10.4143/crt.2025.126. Online ahead of print.

Clinicopathological Factors Influencing PD-L1 Expression and The Effect of Immune Checkpoint Inhibitors on Survival Outcomes in Patients with Gastric Cancer Depending on Sex in a Tertiary Hospital in South Korea

Jeong Hwan Lee  1 , Nayoung Kim  1   2   3 , Ji-Hyun Kim  1 , Hyeon Jeong Oh  4 , Yeejin Kim  1 , Yonghoon Choi  1 , Hyemin Jo  1 , Ho-Kyoung Lee  1 , Jinju Choi  1 , Yu Kyung Jun  1 , Hyuk Yoon  1 , Cheol Min Shin  1 , Young Soo Park  1 , Dong Ho Lee  1   3 , Hye Seung Lee  5 , So Hyun Kang  6 , Young Suk Park  6 , Sang-Hoon Ahn  6 , Yun-Suhk Suh  6 , Do Joong Park  7 , Hyung Ho Kim  6   7 , Ji-Won Kim  1 , Jin Won Kim  1 , Keun-Wook Lee  1   3 , Won Chang  8 , Yoon Jin Lee  8 , Kyoung Ho Lee  8   9 , Young Hoon Kim  8   9 , Soyeon Ahn  10
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Free article

Clinicopathological Factors Influencing PD-L1 Expression and The Effect of Immune Checkpoint Inhibitors on Survival Outcomes in Patients with Gastric Cancer Depending on Sex in a Tertiary Hospital in South Korea

Jeong Hwan Lee et al. Cancer Res Treat. .
Free article

Abstract

Purpose: Programmed cell death ligand-1 (PD-L1) negatively regulates T-cell activation, and exhibits sex-based differences in expression and immune responses. This study investigated sex-related differences in clinicopathological factors influencing PD-L1 expression and the effect of immune checkpoint inhibitors (ICIs) on survival in gastric cancer (GC) patients in South Korea.

Materials and methods: We analyzed a prospective cohort of 468 GC patients who underwent PD-L1 immunohistochemistry. Age, tumor characteristics, molecular features, and survival outcomes were compared by sex. Multivariate analyses, including Cox proportional hazards modeling with an interaction term for sex, were performed.

Results: Among 468 patients, 280 (59.8%) were PD-L1 positive. In the overall cohort, PD-L1 positivity was significantly associated with Epstein-BarrVirus (EBV) infection (odd ratio [OR]=7.46, p<0.001), antral location of GC (OR=1.84, p=0.027), and macrosatellite instability-High (MSI-H) (OR=5.04, p=0.027). Diffuse-type histology was inversely associated (OR=0.22, p=0.041). In males, EBV (OR=36.27) and antral location (OR=2.38) were significant. In females, only MSI-H was significant (OR=11.63). ICI-containing therapy significantly improved survival in males (p=0.012) but not in females (p=0.415). Cox regression showed a survival benefit from ICIs (HR=0.70, p=0.080), with a borderline-significant interaction by sex (p=0.073).

Conclusion: PD-L1 expression and therapeutic efficacy of ICIs differ by sex in GC. EBV infection and antral tumor location were independent factors in males, while MSI-H status was significant in females. These findings highlights the importance of sex-based immunobiology in tailoring GC treatment strategies.

Keywords: B7-H1 Antigen; Immune checkpoint inhibitors; Sex; Stomach neoplasms; Survival.

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