Tumor PDCD1LG2 (PD-L2) Expression and the Lymphocytic Reaction to Colorectal Cancer.
Tumor PDCD1LG2 (PD-L2) Expression and the Lymphocytic Reaction to Colorectal Cancer.
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DOI：
10.1158/2326-6066.cir-17-0122
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发表时间：
2017-11
影响因子：
10.1
通讯作者：
Ogino S
中科院分区：
文献类型：
--
作者：
Masugi Y;Nishihara R;Hamada T;Song M;da Silva A;Kosumi K;Gu M;Shi Y;Li W;Liu L;Nevo D;Inamura K;Cao Y;Liao X;Nosho K;Chan AT;Giannakis M;Bass AJ;Hodi FS;Freeman GJ;Rodig SJ;Fuchs CS;Qian ZR;Nowak JA;Ogino S
免疫检查点配体CD 274（来自基因CD 274的程序性细胞死亡1配体1，PD-L1）的表达有助于抑制各种肿瘤类型中的抗肿瘤T细胞介导的免疫应答。然而，PDCD 1 LG 2（PD-L2，CD 273，来自基因PDCD 1 LG 2）在肿瘤微环境中的作用仍不清楚。我们假设肿瘤PDCD 1 LG 2表达可能与结直肠癌的淋巴细胞反应呈负相关。我们通过免疫组织化学方法检测了两个美国地区823例结肠癌和直肠癌病例中肿瘤PDCD 1 LG 2的表达。根据PDCD 1 LG 2表达癌细胞的百分比，将肿瘤分为四分位数。我们进行了多变量有序逻辑回归分析，以评估肿瘤PDCD 1 LG 2表达与克罗恩样淋巴反应、瘤周淋巴细胞反应、瘤内腺周反应或肿瘤浸润淋巴细胞的相关性，控制潜在的混杂因素，包括微卫星不稳定性、CpG岛甲基化表型、长散布核苷酸元件-1甲基化以及KRAS、BRAF和PIK 3CA突变。肿瘤PDCD 1 LG 2表达与克罗恩样淋巴样反应呈负相关（Ptrend = 0.0003）。对于克罗恩病样淋巴样反应的三层有序分类中的单位增加，PDCD 1 LG 2表达肿瘤细胞百分比的最高（与最低）四分位数的多变量比值比为0.38（95%置信区间，0.22-0.67）。肿瘤PDCD 1 LG 2表达与瘤周淋巴细胞反应、瘤内腺周反应、肿瘤浸润淋巴细胞或患者生存率无关（P趋势>0.13）。因此，肿瘤PDCD 1 LG 2表达与结肠直肠癌的克罗恩样淋巴反应呈负相关，表明表达PDCD 1 LG 2的肿瘤细胞在结肠直肠癌发生过程中抑制三级淋巴组织的发育中可能发挥作用。
Expression of the immune-checkpoint ligand CD274 (programmed cell death 1 ligand 1, PD-L1, from gene CD274) contributes to suppression of antitumor T cell–mediated immune response in various tumor types. However, the role of PDCD1LG2 (PD-L2, CD273, from gene PDCD1LG2) in the tumor microenvironment remains unclear. We hypothesized that tumor PDCD1LG2 expression might be inversely associated with lymphocytic reactions to colorectal cancer. We examined tumor PDCD1LG2 expression by immunohistochemistry in 823 colon and rectal carcinoma cases within two U.S.-nationwide cohort studies and categorized tumors into quartiles according to the percentage of PDCD1LG2–expressing carcinoma cells. We conducted multivariable ordinal logistic regression analysis to assess the associations of tumor PDCD1LG2 expression with Crohn’s-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, or tumor-infiltrating lymphocytes, controlling for potential confounders, including microsatellite instability, CpG island methylator phenotype, long-interspersed nucleotide element-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Tumor PDCD1LG2 expression was inversely associated with Crohn’s-like lymphoid reaction (Ptrend = 0.0003). For a unit increase in the three-tiered ordinal categories of Crohn’s-like lymphoid reaction, a multivariable odds ratio in the highest (vs lowest) quartile of the percentage of PDCD1LG2–expressing tumor cells was 0.38 (95% confidence interval, 0.22–0.67). Tumor PDCD1LG2 expression was not associated with peritumoral lymphocytic reaction, intratumoral periglandular reaction, tumor-infiltrating lymphocytes, or patient survival (Ptrend>0.13). Thus, tumor PDCD1LG2 expression is inversely associated with Crohn’s-like lymphoid reaction to colorectal cancer, suggesting a possible role of PDCD1LG2–expressing tumor cells in inhibiting the development of tertiary lymphoid tissues during colorectal carcinogenesis.