Clinical significance of programmed cell death-ligand 1 expression and the immune microenvironment at the invasive front of colorectal cancers with high microsatellite instability

被引:63
作者
Korehisa, Shotaro [1 ]
Oki, Eiji [1 ]
Iimori, Makoto [2 ]
Nakaji, Yu [1 ,3 ]
Shimokawa, Mototsugu [4 ]
Saeki, Hiroshi [1 ]
Okano, Shinji [5 ]
Oda, Yoshinao [3 ]
Maehara, Yoshihiko [1 ]
机构
[1] Kyushu Univ, Grad Sch Med Sci, Dept Surg & Sci, Fukuoka, Japan
[2] Kyushu Univ, Grad Sch Pharmaceut Sci, Dept Mol Canc Biol, Fukuoka, Japan
[3] Kyushu Univ, Grad Sch Med Sci, Dept Anat Pathol, Pathol Sci, Fukuoka, Japan
[4] Kyushu Natl Canc Ctr, Clin Res Inst, Fukuoka, Japan
[5] Cleveland Clin, Digest Dis & Surg Inst, Dept Gen Surg, Cleveland, OH 44106 USA
关键词
colorectal cancer; high microsatellite instability; programmed cell death-ligand 1 (PD-L1); invasive front; M2-type macrophage; MISMATCH-REPAIR; MESENCHYMAL TRANSITION; PD-L1; EXPRESSION; BRAF MUTATION; UNTREATED MELANOMA; LUNG-CANCER; CARCINOMA; NIVOLUMAB; IMMUNOTHERAPY; SAFETY;
D O I
10.1002/ijc.31107
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Immunotherapy is reportedly effective in colorectal cancers (CRCs) with high microsatellite instability (MSI-H); however, the specific cell types that respond to immune checkpoint therapy are unclear. Herein, we aimed to examine the expression of programmed cell death-ligand 1 (PD-L1) and related proteins in MSI-H and microsatellite-stable (MSS) CRCs to investigate the immune microenvironment at the tumor's invasive front. The MSI status was retrospectively assessed in 499 patients undergoing surgical resection of primary CRC; of these, 48 were classified as MSI-H. Propensity score matching was performed, and tissues from 36 and 37 patients with MSI-H and MSS CRCs, respectively, were immunohistochemically evaluated for PD-L1, PD-1, CD8 and CD68. PD-L1 expression was evaluated separately for tumor cells (PD-L1 [T]) and tumor-infiltrating myeloid cells in the stroma (PD-L1 [I]). PD-L1 (T) was positive in only 5.4% and 36.1% of MSS and MSI-H CRCs, while PD-L1 (I) was positive in 27% and 72.2% of these CRCs, respectively. The PD-L1 (T) and PD-L1 (I) expression levels in MSI-H CRCs significantly correlated with poor differentiation, lymphatic invasion and vascular invasion (p<0.05), and with early-stage adenocarcinoma and high budding grade (p<0.05), respectively. Significantly more PD-L1 (I), CD8-positive cells and CD68-positive macrophages were present at the invasive front than in the central tumor in MSI-H CRCs (p<0.005). PD-L1 was expressed on both tumor cells and CD68/CD163-positive (M2) macrophages at the invasive front of MSI-H CRCs. In conclusion, PD-L1-positive tumor cells and M2-type tumor-associated macrophages may contribute to tumor invasion and immune escape at the invasive front.
引用
收藏
页码:822 / 832
页数:11
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