BRAF V600E 突变转移性结直肠癌中 PD-L1、PD-L2 表达与 TIL（肿瘤浸润淋巴细胞）的关联：GI-SCREEN 事后分析

The programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1)/programmed cell death-ligand 2 (PD-L2) axis is responsible for cancer immune escape, which facilitates disease progression. However, the role of PD-L1 and PD-L2 and tumor-infiltrating lymphocytes (TILs) in metastatic colorectal cancer (mCRC) has not been studied.

We conducted a post-hoc analysis of the Nationwide Cancer Genome Screening Project GI-SCREEN in mCRC. PD-L1 (22C3) and PD-L2 (MEB123.3G2.038) expression in formalin-fixed paraffin-embedded tumor samples was centrally assessed by immunohistochemical assays. TILs were morphologically evaluated using hematoxylin and eosin staining. Clinical information was extracted from the GI-SCREEN database. Inclusion of patients with BRAF V600E mutation was prioritized.

Two hundred patients with mCRC (median age 65 years and 116 males) were included in the study. Genomic testing identified RAS mutations in 87 (44%) patients, BRAF V600E mutations in 27 (14%), and microsatellite instability-high status in 8 (4%). Positivity of PD-L1 and PD-L2 was 11% and 47% on tumor cells (TC) and 0% and 64% on immune cells, respectively, and that was associated with the presence of TILs ( P = 0.011 for PD-L1, 0.024 for PD-L2). PD-L1+ TC was significantly more frequent in BRAF V600E-mutated tumors ( P = 0.03). Even in microsatellite stable tumors, BRAF V600E-mutated tumors were significantly associated with higher expression of PD-L1 on TC than BRAF wild-type (25% versus 8%, P = 0.02).

Our study showed a distinct pattern of PD-L1 expression on TC of patients with BRAF V600E-mutated mCRC, which could be a potential therapeutic target for PD-1 blockade.