Abstract 6032: Subtypes of cancer-associated fibroblasts, myCAF, iCAF, and apCAF, might be associated with adverse prognostic signature of patients with gastric cancer

Abstract Background: It has been reported that the tumor microenvironment (TME) may play an important role for the progression of various carcinomas, including gastric cancer (GC). The cancer-associated fibroblast (CAF) is one of major stromal components of TME. CAF includes 3 subtypes such as myofibroblastic CAF (myCAF), inflammatory CAF (iCAF), and antigen-presenting CAF (apCAF). In this study, we investigated the clinicopathologic significance of 3 CAF subtypes in GC. Methods: A total of 1330 GC specimens was collected in this study. Immunohistochemical study was performed using 3 antibodies against myCAF, iCAF, and apCAF. Staining level of fibroblasts was scored using a semi-quantitative combined score (from 0 to 6) which was obtained by the addiction of intensity score (0 to 3) and the proportion score (0-3). Results: myCAFs were found significantly (p0.05) frequent in GC patients with advanced T stage, high lymphatic invasion, and high venous invasion. apCAFs were found significantly (p0.05) frequent in GC patients with advanced T stage, lymphatic metastasis, distant metastasis, and postoperative recurrence. In contrast, iCAF showed significantly (p0.05) lower in GC patients with tumor infiltration and few postoperative recurrence. Univariable Cox indicated that myCAF+ showed significantly shorter overall survival (OS; HR 1.97, 95%CI 1.34-2.90, p0.001), iCAF+ showed significantly shorter OS (HR 1.29, 1.04-1.61, p=0.022), and apCAF+ showed significantly shorter OS (HR 1.26, 1.03-1.54, p=0.027). After adjustment for age, sex, T/N/M stage, histology, cytology, and lymphatic invasion, only myCAF+ remained to be independent prognostic factor for OS (HR 1.56, 1.04-2.34, p=0.032), whereas iCAF+ and apCAF+ were not (p0.05). The triple-positive signature of myCAF, iCAF, and apCAF+) conferred significantly (p0.001) high risk for OS (univariable Cox HR 2.98, 95%CI 1.83-4.83; multivariate Cox HR 2.48, 95%CI 1.51-4.06). Conclusions: In this GC cohort, myCAF, iCAF, and apCAF are individually associated with lower survival, and myCAF, iCAF, and apCAF defined an independent adverse prognostic signature. Cooperative stromal programs might provide rationale for CAF subtype status as a prognostic factor. CAF subtypes might be associated with adverse prognostic signature of GC patients. Citation Format: DONGHENG MA, Hinano Nishikubo, Tomoya Sano, Daiki Imanishi, Takashi Sakuma, Canfeng Fan, Yurie Yamamoto, Masakazu Yashiro. Subtypes of cancer-associated fibroblasts, myCAF, iCAF, and apCAF, might be associated with adverse prognostic signature of patients with gastric cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6032.