FAT4 mutation as a potential predictive biomarker for immunotherapy combined with anti-angiogenic therapy in MSS metastatic colorectal cancer.

• DOI: 10.1200/jco.2022.40.16_suppl.e15504
• Publication Date: 2022-06-06T16:16:17Z
• Authors: Mifen Chen; Qi Zhang; Hui Chen; Zhenghang Wang; Ting Xu; Changsong QI; Shiqing Chen; Xiaochen Zhao; Yuezong Bai; Zhi Peng; Xicheng Wang; Xiaotian Zhang; Jifang Gong; Lin Shen; Jian Li
• Keywords: Microsatellite Instability

e15504 Background: Microsatellite stable (MSS) metastatic colorectal cancer (CRC) lacks effective treatments and has a poor prognosis. The aim of this study was to identify patients who could benefit from immunotherapy combined with anti-angiogenic therapy. Exploration predictive biomarkers help maximize the clinical benefits. Methods: In total, FFPE tissues samples before therapy 21 were successfully tested for tumor microenvironments (TMEs) by multiple immunofluorescence, which 11 them detected 733-gene NGS panel in CLIA-certified laboratory. correlation between gene variations durable (DCB: PR, or SD≥6 months), PFS TMEs analyzed Fisher's test, K-M survival curve analysis Mann Whitney respectively. Results: Significant difference FAT4 mutation (FAT4-MUT) wildtype (FAT4-WT) regarding DCB (100%, 4/4 vs 17%, 1/7, P = 0.0152) progress-free (median PFS, 13.8 months 2.8 months, LogRank 0.003). There no significant TMB level NDB (SD＜6 PD) groups (12 mut/Mb 6 mut/Mb, 0.0823) FAT4-MUT FAT4-WT (11 0.3697). analyses revealed that CD3+CD4+ T cell proportion tended be higher (0.7% 0.3%, 0.054). Further TIMER2.0 data showed significantly associated Immune infiltration four immune cells, including CD4+ both colon rectal adenocarcinoma, CD8+ central memory cell, B Macrophage adenocarcinoma. Conclusions: Our findings indicated serves as potential novel biomarker correlated better response MSS CRC, may related activation CD4 infiltration. However, these need validated further cohort expansion.