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Immunosuppressive tumor microenvironment in occupational cholangiocarcinoma: Supportive evidence for the efficacy of immune checkpoint inhibitor therapy
Author(s) -
Sato Yasunori,
Tanaka Shogo,
Kinoshita Masahiko,
Takemura Shigekazu,
Shinkawa Hiroji,
Kokudo Takashi,
Hasegawa Kiyoshi,
Tanaka Hiromu,
Yoshimoto Hidero,
Mori Akira,
Yamamura Minako,
Sasaki Motoko,
Harada Kenichi,
Kubo Shoji
Publication year - 2020
Publication title -
journal of hepato‐biliary‐pancreatic sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.63
H-Index - 60
eISSN - 1868-6982
pISSN - 1868-6974
DOI - 10.1002/jhbp.788
Subject(s) - foxp3 , tumor microenvironment , immune checkpoint , medicine , immune system , nivolumab , microsatellite instability , cancer research , msh2 , tigit , immunology , immunotherapy , oncology , cancer , biology , colorectal cancer , dna mismatch repair , allele , biochemistry , microsatellite , gene
Background Occupational cholangiocarcinoma (CCA) was first described in patients who were working at a printing company in Osaka, Japan. Recently, the therapeutic efficacy and safety of a PD1 inhibitor nivolumab are being evaluated in patients with occupational CCA in an investigator‐initiated clinical trial. The therapeutic effects of immune checkpoint inhibitors are closely associated with immune cells. Methods Immunohistochemical analysis was performed to characterize immune cells in the tumor microenvironment of occupational CCA. The status of mismatch repair (MMR)/microsatellite instability (MSI) was also examined. Results The tumor stroma of occupational CCA was characterized by abundant infiltration of immune cells expressing CD3, CD4, CD8, CD163, FOXP3, and granzyme B. Additionally, lymphocytes expressing immune checkpoint receptors, such as PD1, CTLA4, LAG3, TIM3, and TIGIT, were frequently infiltrated. The loss of immunohistochemical expression of the MMR proteins (MLH1, MSH2, PMS2, and MSH6) was not observed in cases of occupational CCA, and MSI was not detected. Conclusions The tumor microenvironment of occupational CCA had features of immunosuppression, and the occurrence of T‐cell dysfunction or exhaustion was suggested. The results provide supportive evidence for the efficacy of immune checkpoint inhibitor therapy for this disease.