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  3. Tumor PDCD1LG2 (PD-L2) Expression and the Lymphocytic Reaction to Colorectal Cancer

Tumor PDCD1LG2 (PD-L2) Expression and the Lymphocytic Reaction to Colorectal Cancer

  • Cancer Immunol Res. 2017 Nov;5(11):1046-1055. doi: 10.1158/2326-6066.CIR-17-0122.
Yohei Masugi 1 2,  Reiko Nishihara 1 2 3 4 5 6,  Tsuyoshi Hamada 1 2,  Mingyang Song 4 7 8,  Annacarolina da Silva 1 2,  Keisuke Kosumi 1 2,  Mancang Gu 1 2,  Yan Shi 1 2,  Wanwan Li 1 2,  Li Liu 1 2 4 9,  Daniel Nevo 5 6,  Kentaro Inamura 10,  Yin Cao 4 7 8,  Xiaoyun Liao 1 11,  Katsuhiko Nosho 12,  Andrew T Chan 7 8 13,  Marios Giannakis 1 14 15,  Adam J Bass 1 14 15,  F Stephen Hodi 1 11,  Gordon J Freeman 1,  Scott J Rodig 2 16,  Charles S Fuchs 17 18 19,  Zhi Rong Qian 20 2,  Jonathan A Nowak 2 3,  Shuji Ogino 20 2 3 5
Affiliations

Affiliations

  • 1 Department of Medical Oncology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts.
  • 2 Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • 3 Division of MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
  • 4 Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
  • 5 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
  • 6 Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
  • 7 Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts.
  • 8 Division of Gastroenterology, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts.
  • 9 Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan, P.R. China.
  • 10 Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
  • 11 Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • 12 Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
  • 13 Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
  • 14 Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
  • 15 Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
  • 16 Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
  • 17 Yale Cancer Center, New Haven, Connecticut.
  • 18 Department of Medicine, Yale School of Medicine, New Haven, Connecticut.
  • 19 Smilow Cancer Hospital, New Haven, Connecticut.
  • 20 Department of Medical Oncology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts. shuji_ogino@dfci.harvard.edu zhirong_qian@dfci.harvard.edu.
PMID: 29038297 DOI: 10.1158/2326-6066.CIR-17-0122
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. Cancer Immunol Res; 5(11); 1046-55. ©2017 AACR.

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