The critical role of CD4+ T cells in PD-1 blockade against MHC-II-expressing tumors such as classic Hodgkin lymphoma
| Autor: | Hiroyoshi Nishikawa, Joji Nagasaki, Masato Sugano, Masayuki Hino, Yuuki Ohara, Makiko Itami, Masahiro Takeuchi, Nobuhiko Yamauchi, Yosuke Togashi, Junichiro Yuda, Hirohisa Nakamae, Yosuke Minami, Takeaki Sugawara |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Combination therapy medicine.drug_class Programmed Cell Death 1 Receptor chemical and pharmacologic phenomena CD8-Positive T-Lymphocytes Monoclonal antibody Major histocompatibility complex 03 medical and health sciences Mice 0302 clinical medicine MHC class I medicine Tumor Microenvironment Cytotoxic T cell Animals Tumor microenvironment Lymphoid Neoplasia biology Chemistry Histocompatibility Antigens Class II Hematology Hodgkin Disease Blockade 030104 developmental biology 030220 oncology & carcinogenesis biology.protein Cancer research CD8 |
| Zdroj: | Blood Adv |
| ISSN: | 2473-9537 |
| Popis: | Classic Hodgkin lymphoma (cHL) responds markedly to PD-1 blockade therapy, and the clinical responses are reportedly dependent on expression of major histocompatibility complex class II (MHC-II). This dependence is different from other solid tumors, in which the MHC class I (MHC-I)/CD8+ T-cell axis plays a critical role. In this study, we investigated the role of the MHC-II/CD4+ T-cell axis in the antitumor effect of PD-1 blockade on cHL. In cHL, MHC-I expression was frequently lost, but MHC-II expression was maintained. CD4+ T cells highly infiltrated the tumor microenvironment of MHC-II–expressing cHL, regardless of MHC-I expression status. Consequently, CD4+ T-cell, but not CD8+ T-cell, infiltration was a good prognostic factor in cHL, and PD-1 blockade showed antitumor efficacy against MHC-II–expressing cHL associated with CD4+ T-cell infiltration. Murine lymphoma and solid tumor models revealed the critical role of antitumor effects mediated by CD4+ T cells: an anti-PD-1 monoclonal antibody exerted antitumor effects on MHC-I−MHC-II+ tumors but not on MHC-I−MHC-II− tumors, in a cytotoxic CD4+ T-cell–dependent manner. Furthermore, LAG-3, which reportedly binds to MHC-II, was highly expressed by tumor-infiltrating CD4+ T cells in MHC-II–expressing tumors. Therefore, the combination of LAG-3 blockade with PD-1 blockade showed a far stronger antitumor immunity compared with either treatment alone. We propose that PD-1 blockade therapies have antitumor effects on MHC-II–expressing tumors such as cHL that are mediated by cytotoxic CD4+ T cells and that LAG-3 could be a candidate for combination therapy with PD-1 blockade. |
| Databáze: | OpenAIRE |
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