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Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment

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World Journal of Gastroenterology 2023年第40期29卷 5566-5581页

作者： Aitoshi Hoshimoto Atsushi Tatsuguchi Ryohei Hamakubo Takayoshi Nishimoto Jun Omori Naohiko Akimoto Shu Tanaka Shunji Fujimori Tsutomu Hatori Akira Shimizu Katsuhiko Iwakiri Department of Gastroenterology Nippon Medical SchoolTokyo 113-8603Japan Department of Analytic Human Pathology Nippon Medical SchoolTokyo 113-8603Japan Department of Pathology Nippon Medical SchoolChiba Hokusoh HospitalChiba 270-1694Japan

BACKGROUND Comprehensive genomic analysis has shown that small bowel adenocarcinoma(SBA)has different genomic profiles from gastric and colorectal cancers.Hence,it is essential to establish chemotherapeutic regimens based on SBA characteristics.The expression of programmed cell death-ligand 1(PD-L1)and programmed cell death-ligand 2(PD-L2)in SBA is not fully understood.Anti-PD-L1/PD-1 therapy uses tumor-infiltrating lymphocytes(TILs);therefore,the status of TILs in the tumor microenvironment(TME)may influence their efficacy.The ratio of FoxP3+to CD8+T cells has been reported to be useful in predicting the prognosis of digestive system cancers.AIM To investigate the clinicopathological significance of PD-L1/2 expression according to the status of TILs in SBA tissues.METHODS We performed immunohistochemical analysis for PD-L1,PD-L2,CD8,FoxP3,and DNA mismatch repair(MMR)proteins using formalin-fixed,paraffin-embedded tissues from 50 patients diagnosed with primary SBA.The immunoreactivities of PD-L1 and PD-L2 were determined separately in tumor cells and tumor-infiltrating immune cells throughout the tumor center and invasive margins,and finally evaluated using the combined positive score(CPS).We assessed CD8+and FoxP3+T cells in the intratumoral and tumor-surrounding stroma.Subsequently,we calculated and summed the ratio of FoxP3 to CD8+T cell counts.Immune-related cell densities were graded as low or high.Immunohistochemical results were compared with clinicopathological factors and patient prognosis.The distribution of cancer-specific survival(CSS)was estimated using the Kaplan–Meier method,and the log-rank test was used to test for significant differences in CSS.A Cox proportional hazard model was also used to assess the effect of tumor variables on CSS.RESULTS PD-L1 expression was positive in 34%in tumor cells(T-PD-L1)and 54%in tumor-infiltrating immune cells(I-PDL1)of the cases examined.T-PD-L2 was positive in 34%and I-PD-L2 was positive in 42%of the cases.PD-L1 CPS≥10 and PD-L2 CPS≥10 were observed in 50%and

关键词： Small bowel adenocarcinoma programmed cell death-ligand 1 programmed cell death-ligand 2 Tumor microenvironment Tumor-infiltrating lymphocytes Regulatory T-cells

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