Liver metastasis affects progression pattern during immune checkpoint inhibitors monotherapy in gastric cancer

Iori Motoo; Takayuki Ando; Takeru Hamashima; Shinya Kajiura; Miho Sakumura; Yuko Ueda; Aiko Murayama; Kohei Ogawa; Kenichiro Tsukada; Akira Ueda; Nobuhiro Suzuki; Naokatsu Nakada; Koji Nakashima; Ayumu Hosokawa; Ichiro Yasuda

doi:10.3389/fonc.2023.1193533

Liver metastasis affects progression pattern during immune checkpoint inhibitors monotherapy in gastric cancer

Front Oncol. 2023 Sep 15:13:1193533. doi: 10.3389/fonc.2023.1193533. eCollection 2023.

Authors

Affiliations

¹ Third Department of Internal Medicine, University of Toyama, Toyama, Japan.
² Department of Pathology, University of Toyama, Toyama, Japan.
³ Department of Gastroenterology, Toyama Prefectural Central Hospital, Toyama, Japan.
⁴ Department of Gastroenterology, Kouseiren Takaoka Hospital, Takaoka, Japan.
⁵ Department of Medical Oncology, Toyama Red Cross Hospital, Toyama, Japan.
⁶ Department of Gastroenterology, Jouetsu Sogo Hospital, Jouetsu, Japan.
⁷ Department of Gastroenterology, Itoigawa Sogo Hospital, Itoigawa, Japan.
⁸ Department of Clinical Oncology, University of Miyazaki Hospital, Miyazaki, Japan.

Abstract

Introduction: The efficacy of immune checkpoint inhibitors (ICIs) is heterogeneous at each metastatic site, and tumor progression pattern is associated with survival; however, it remains unclear in gastric cancer (GC). Therefore, we aimed to clarify the progression pattern in response to ICIs in patients with GC, and we analyzed its mechanism focusing on the intratumoral immune cells.

Methods: Patients who received ICIs were retrospectively classified into non-systemic and systemic progression groups based on their radiological assessments. Moreover, the best percentage change in target lesions from each organ was compared.

Results: Among 148 patients, the non-systemic progression group showed a significant improvement in overall survival (OS) compared with the systemic progression group (median, 5.6 months vs. 3.3 months; HR, 0.53; 95%CI, 0.32-0.89; p = 0.012). Poor performance status (HR, 1.73, 95%CI, 1.00-2.87) and systemic progression (HR, 3.09, 95%CI, 1.95-4.82) were associated with OS. Of all metastatic sites, the liver showed the poorest percentage change, and liver metastasis (OR, 2.99, 95%CI, 1.04-8.58) was associated with systemic progression. Hence, intratumoral CD8+ T-cell density was lower in patients with liver metastasis than in those without liver metastasis after ICIs, although the density of CD4+ T-cells (Th1, Th17, and Treg) and CD163+ cells (TAM) were not significantly different.

Conclusion: The new progression pattern was associated with OS in GC. Liver metastasis may be a predictive factor of systemic progression during ICIs by regulating intratumoral CD8+ T-cells.

Keywords: gastric cancer; immune checkpoint inhibitor; liver metastasis; progression pattern; tumor-infiltrating lymphocytes.