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The critical role of CD4+T cells in PD-1 blockade against MHC-II–expressing tumors such as classic Hodgkin lymphoma
- Source :
- Blood Advances; September 2020, Vol. 4 Issue: 17 p4069-4082, 14p
- Publication Year :
- 2020
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 24739529 and 24739537
- Volume :
- 4
- Issue :
- 17
- Database :
- Supplemental Index
- Journal :
- Blood Advances
- Publication Type :
- Periodical
- Accession number :
- ejs56365460
- Full Text :
- https://doi.org/10.1182/bloodadvances.2020002098