PD-L1/L2 protein levels rapidly increase on monocytes via trogocytosis from tumor cells in classical Hodgkin lymphoma.

Abstract

In classical Hodgkin lymphoma (cHL)-characterized by the presence of Hodgkin and Reed-Sternberg (HRS) cells-tumor-associated macrophages (TAMs) play a pivotal role in tumor formation. However, the significance of direct contact between HRS cells and TAMs has not been elucidated. HRS cells and TAMs are known to express PD-L1, which leads to PD-1+ CD4+ T cell exhaustion in cHL. Here, we found that PD-L1/L2 expression was elevated in monocytes co-cultured with HRS cells within 1 h, but not in monocytes cultured with supernatants of HRS cells. Immunofluorescence analysis of PD-L1/L2 revealed that their upregulation resulted in membrane transfer called "trogocytosis" from HRS cells to monocytes. PD-L1/L2 upregulation was not observed in monocytes co-cultured with PD-L1/L2-deficient HRS cells, validating the hypothesis that there is a direct transfer of PD-L1/L2 from HRS cells to monocytes. In the patients, both ligands (PD-L1/L2) were upregulated in TAMs in contact with HRS cells, but not in TAMs distant from HRS cells, suggesting that trogocytosis occurs in cHL patients. Taken together, trogocytosis may be one of the mechanisms that induces rapid upregulation of PD-L1/L2 in monocytes to evade antitumor immunity through the suppression of T cells as mediated by MHC antigen presentation.

• Authors: Masaharu Kawashima, Joaquim Carreras, Hiroshi Higuchi, Ryutaro Kotaki, Takahiro Hoshina, Kazuki Okuyama, Naoto Suzuki, Masatoshi Kakizaki, Yuji Miyatake, Kiyoshi Ando, Masafumi Nakayama, Shinjiro Umezu, Ryouichi Horie, Yuriko Higuchi, Koko Katagiri, Susumu Goyama, Toshio Kitamura, Kenji Chamoto, Shingo Yano, Naoya Nakamura, Ai Kotani
• Journal: Leukemia (Leukemia) Vol. 34 Issue 9 Pg. 2405-2417 (09 2020) ISSN: 1476-5551 [Electronic] England
• PMID: 32089543 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• B7-H1 Antigen
• CD274 protein, human
• PDCD1LG2 protein, human
• Programmed Cell Death 1 Ligand 2 Protein

Topics

• B7-H1 Antigen (metabolism)
• Cell Line, Tumor
• Cell Movement
• Hodgkin Disease (immunology, metabolism, pathology)
• Humans
• Major Histocompatibility Complex (immunology)
• Monocytes (metabolism)
• Programmed Cell Death 1 Ligand 2 Protein (metabolism)
• Tumor Microenvironment (immunology)