Distinct tumor immune microenvironments in primary and metastatic lesions in gastric cancer patients
Seung-Myoung Son, Chang Gok Woo, Dae Hoon Kim, Hyo Yung Yun, Hong-Sik Kim, Hee Kyung Kim, Yaewon Yang, Jihyun Kwon, Minsuk Kwon, Tae Yong Kim, Hyung-Don Kim, June‐Young Koh, Su‐Hyung Park, Eui‐Cheol Shin, Hye Sook Han
Abstract
Abstract This study compared the tumor immune microenvironments (TIMEs) of primary gastric cancer (PGC) and paired metastatic gastric cancer (MGC). CD4 + and CD8 + T-cell density and PD-L1 expression were evaluated by multiplex immunohistochemistry, DNA mismatch repair (MMR) by immunohistochemistry, and immune-related genes by RNA sequencing. Twenty-three patients who underwent surgical treatment for PGC and MGC were enrolled in this study. CD8 + T-cell, PD-L1 + cell, and PD-L1 + CK + cell densities were significantly lower in MGC than PGC. PD-L1 positivity using a combined positive score (≥ 1%) and deficient MMR were observed in 52.2% and 8.7% of PGC samples, respectively, whereas both occurred in only 4.3% of MGC samples. The most frequent TIME types were inflamed (34.8%) and adaptive immune resistance (34.8%) in PGC, and immune desert (65.2%) and immunological ignorance (73.9%) in MGC. In transcriptome analysis, the expression of the T-cell inflamed gene set and co-stimulatory gene module was down-regulated in MGC compared to PGC. The total CD8 + T-cell density was an independent prognostic marker in both PGC and MGC (univariate P = 0.002, multivariate P = 0.006). Our result suggest that the TIME of metastatic tumors was less immunologically active compared to that of primary tumors in gastric cancer patients.