Immunosuppressive tumor microenvironment in occupational cholangiocarcinoma: Supportive evidence for the efficacy of immune checkpoint inhibitor therapy.

Abstract

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.

• Authors: Yasunori Sato, Shogo Tanaka, Masahiko Kinoshita, Shigekazu Takemura, Hiroji Shinkawa, Takashi Kokudo, Kiyoshi Hasegawa, Hiromu Tanaka, Hidero Yoshimoto, Akira Mori, Minako Yamamura, Motoko Sasaki, Kenichi Harada, Shoji Kubo
• Journal: Journal of hepato-biliary-pancreatic sciences (J Hepatobiliary Pancreat Sci) Vol. 27 Issue 11 Pg. 860-869 (Nov 2020) ISSN: 1868-6982 [Electronic] Japan
• PMID: 32506715 (Publication Type: Journal Article)
• Copyright: © 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Chemical References

• Immune Checkpoint Inhibitors

Topics

• Bile Duct Neoplasms (drug therapy)
• Bile Ducts, Intrahepatic
• Cholangiocarcinoma (drug therapy)
• Humans
• Immune Checkpoint Inhibitors
• Microsatellite Instability
• Tumor Microenvironment