Tumor PDCD1LG2 (PD-L2) expression and the lymphocytic reaction to colorectal cancer

Yohei Masugi, Reiko Nishihara, Tsuyoshi Hamada, Mingyang Song, Annacarolina Da Silva, Keisuke Kosumi, Mancang Gu, Yan Shi, Wanwan Li, Li Liu, Daniel Nevo, Kentaro Inamura, Yin Cao, Xiaoyun Liao, Katsuhiko Nosho, Andrew T. Chan, Marios Giannakis, Adam J. Bass, F. Stephen Hodi, Gordon J. FreemanScott J. Rodig, Charles S. Fuchs, Zhi Rong Qian, Jonathan A. Nowak, Shuji Ogino

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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 IHC 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-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-like lymphoid reaction (Ptrend = 0.0003). For a unit increase in the three-tiered ordinal categories of Crohn-like lymphoid reaction, a multivariable OR 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-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.

Original languageEnglish
Pages (from-to)1046-1055
Number of pages10
JournalCancer immunology research
Volume5
Issue number11
DOIs
Publication statusPublished - 2017 Nov 1
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

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  • Cite this

    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, A. T., Giannakis, M., Bass, A. J., Hodi, F. S., ... Ogino, S. (2017). Tumor PDCD1LG2 (PD-L2) expression and the lymphocytic reaction to colorectal cancer. Cancer immunology research, 5(11), 1046-1055. https://doi.org/10.1158/2326-6066.CIR-17-0122