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. Freeman & 5 others Scott J. Rodig, Charles S. Fuchs, Zhi Rong Qian, Jonathan A. Nowak, Shuji Ogino

Research output: Contribution to journalArticle

12 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

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Colorectal Neoplasms
Neoplasms
Tumor-Infiltrating Lymphocytes
CD274 Antigen
Long Interspersed Nucleotide Elements
Carcinoma
Microsatellite Instability
CpG Islands
Tumor Microenvironment
Lymphoid Tissue
Methylation
Genes
Colon
Carcinogenesis
Cohort Studies
Logistic Models
Regression Analysis
Confidence Intervals
Ligands
Phenotype

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

Cite this

Tumor PDCD1LG2 (PD-L2) expression and the lymphocytic reaction to colorectal cancer. / Masugi, Yohei; Nishihara, Reiko; Hamada, Tsuyoshi; Song, Mingyang; Da Silva, Annacarolina; Kosumi, Keisuke; Gu, Mancang; Shi, Yan; Li, Wanwan; Liu, Li; Nevo, Daniel; Inamura, Kentaro; Cao, Yin; Liao, Xiaoyun; Nosho, Katsuhiko; Chan, Andrew T.; Giannakis, Marios; Bass, Adam J.; Hodi, F. Stephen; Freeman, Gordon J.; Rodig, Scott J.; Fuchs, Charles S.; Qian, Zhi Rong; Nowak, Jonathan A.; Ogino, Shuji.

In: Cancer immunology research, Vol. 5, No. 11, 01.11.2017, p. 1046-1055.

Research output: Contribution to journalArticle

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 2017, 'Tumor PDCD1LG2 (PD-L2) expression and the lymphocytic reaction to colorectal cancer', Cancer immunology research, vol. 5, no. 11, pp. 1046-1055. https://doi.org/10.1158/2326-6066.CIR-17-0122
Masugi, Yohei ; Nishihara, Reiko ; Hamada, Tsuyoshi ; Song, Mingyang ; Da Silva, Annacarolina ; Kosumi, Keisuke ; Gu, Mancang ; Shi, Yan ; Li, Wanwan ; Liu, Li ; Nevo, Daniel ; Inamura, Kentaro ; Cao, Yin ; Liao, Xiaoyun ; Nosho, Katsuhiko ; Chan, Andrew T. ; Giannakis, Marios ; Bass, Adam J. ; Hodi, F. Stephen ; Freeman, Gordon J. ; Rodig, Scott J. ; Fuchs, Charles S. ; Qian, Zhi Rong ; Nowak, Jonathan A. ; Ogino, Shuji. / Tumor PDCD1LG2 (PD-L2) expression and the lymphocytic reaction to colorectal cancer. In: Cancer immunology research. 2017 ; Vol. 5, No. 11. pp. 1046-1055.
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AU - Song, Mingyang

AU - Da Silva, Annacarolina

AU - Kosumi, Keisuke

AU - Gu, Mancang

AU - Shi, Yan

AU - Li, Wanwan

AU - Liu, Li

AU - Nevo, Daniel

AU - Inamura, Kentaro

AU - Cao, Yin

AU - Liao, Xiaoyun

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AU - Chan, Andrew T.

AU - Giannakis, Marios

AU - Bass, Adam J.

AU - Hodi, F. Stephen

AU - Freeman, Gordon J.

AU - Rodig, Scott J.

AU - Fuchs, Charles S.

AU - Qian, Zhi Rong

AU - Nowak, Jonathan A.

AU - Ogino, Shuji

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