PMID- 36894899 OWN - NLM STAT- MEDLINE DCOM- 20230313 LR - 20230313 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 23 IP - 1 DP - 2023 Mar 9 TI - Characterisation of tumor microenvironment and prevalence of CD274/PD-L1 genetic alterations difference in colorectal Cancer. PG - 221 LID - 10.1186/s12885-023-10610-1 [doi] LID - 221 AB - BACKGROUND: Large-scale genomic alterations, especially CD274/PD-L1 gene amplification, have great impact on anti-PD-1 efficacy on cancers such as Hodgkin's lymphoma. However, the prevalence of PD-L1 genetic alterations in colorectal cancer (CRC) and its correlation with the tumor immune microenvironment and clinical implications remain unknown. MATERIALS AND METHODS: PD-L1 genetic alterations were evaluated in 324 patients with newly diagnosed CRC including 160 mismatch repair-deficient (dMMR) patients and 164 mismatch repair-proficient (pMMR) patients using fluorescence in situ hybridization (FISH) method. The correlation between PD-L1 and the expression of the common immune markers was analyzed. RESULTS: Totally 33 (10.2%) patients were identified with aberrant PD-L1 genetic alternations including deletion (2.2%), polysomy (4.9%), and amplification (3.1%); They had more aggressive features such as advanced stage (P = 0.02), shorter overall survival (OS) (P < 0.001) than patients with disomy. The aberrations correlated with positive lymph node (PLN) (p = 0.001), PD-L1 expression by immunohistochemistry (IHC) in tumor cells (TCs) or tumor-infiltrated immunocytes (ICs) (both p < 0.001), and pMMR (p = 0.029). When dMMR and pMMR were analyzed independently, the correlations of aberrant PD-L1 genetic alterations with PD-1 expression (p = 0.016), CD4 + T cells (p = 0.032), CD8 T + cells (p = 0.032) and CD68 + cells (p = 0.04) were only found in dMMR cohort. CONCLUSIONS: The prevalence of PD-L1 genetic alterations was relatively low in CRC, but the aberrations usually correlate with aggressive nature. The correlation between PD-L1 genetic alterations and tumor immune features was only observed in dMMR CRC. CI - (c) 2023. The Author(s). FAU - Yang, Lin AU - Yang L AD - Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, 1838 Baiyun Avenue North, Guangzhou, 510515, China. FAU - Liu, Shousheng AU - Liu S AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road east, Guangzhou, 510060, China. AD - Department of General Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road east, Guangzhou, 510060, China. FAU - He, Wenzhuo AU - He W AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road east, Guangzhou, 510060, China. AD - Department of General Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road east, Guangzhou, 510060, China. FAU - Xiong, Zhenchong AU - Xiong Z AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road east, Guangzhou, 510060, China. xiongzhch@sysucc.org.cn. AD - Department of Breast Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road east, Guangzhou, 510060, China. xiongzhch@sysucc.org.cn. FAU - Xia, Liangping AU - Xia L AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road east, Guangzhou, 510060, China. xialp@sysucc.org.cn. AD - Department of General Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road east, Guangzhou, 510060, China. xialp@sysucc.org.cn. LA - eng GR - 82002557/National Natural Science Foundation of China/ GR - 82102995/National Natural Science Foundation of China/ PT - Journal Article DEP - 20230309 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (B7-H1 Antigen) RN - 0 (CD274 protein, human) RN - Turcot syndrome SB - IM MH - Humans MH - *B7-H1 Antigen/genetics/metabolism MH - Tumor Microenvironment/genetics MH - In Situ Hybridization, Fluorescence MH - Prevalence MH - *Colorectal Neoplasms/epidemiology/genetics MH - DNA Mismatch Repair/genetics PMC - PMC9996909 OTO - NOTNLM OT - Fluorescence in situ hybridization OT - Immune microenvironment OT - Mismatch repair deficiency OT - PD-L1 OT - Prognosis COIS- The authors have no conflict of interest to declare. EDAT- 2023/03/10 06:00 MHDA- 2023/03/14 06:00 PMCR- 2023/03/09 CRDT- 2023/03/09 23:34 PHST- 2022/09/20 00:00 [received] PHST- 2023/02/06 00:00 [accepted] PHST- 2023/03/09 23:34 [entrez] PHST- 2023/03/10 06:00 [pubmed] PHST- 2023/03/14 06:00 [medline] PHST- 2023/03/09 00:00 [pmc-release] AID - 10.1186/s12885-023-10610-1 [pii] AID - 10610 [pii] AID - 10.1186/s12885-023-10610-1 [doi] PST - epublish SO - BMC Cancer. 2023 Mar 9;23(1):221. doi: 10.1186/s12885-023-10610-1.