Monalizumab efficacy correlates with HLA-E surface expression and NK cell activity in head and neck squamous carcinoma cell lines

Abstract

PurposeNKG2A, an inhibitory receptor expressed on NK cells and T cells, leads to immune evasion by binding to HLA-E expressed on cancer cells. Here, we investigated the relationship between HLA-E surface expression on head and neck squamous cell carcinoma (HNSCC) cell lines and the e cacy of monalizumab, an NKG2A inhibitor, in promoting NK cell activity. MethodsSix HNSCC cell lines were used as target cells. After exposure to IFN-γ, HLA-E surface expression on HNSCC cell lines was measured by ow cytometry. Peripheral blood mononuclear cells (PBMCs) from healthy donors and isolated NK cells were used as effector cells. NK cells were stimulated by treatment with IL-2 and IL-15 for 5 days, and NK cell-induced cytotoxicity was analyzed by CD107a degranulation and 51 Cr release assays. ResultsWe con rmed that HLA-E expression was increased by IFN-γ secreted by NK cells and that HLA-E expression was different for each cell line upon exposure to IFN-γ. Cell lines with high HLA-E expression showed stronger inhibition of NK cell cytotoxicity, and e cacy of monalizumab was high. Combination with cetuximb increased the e cacy of monalizumab. In addition, stimulation of isolated NK cells with IL-2 and IL-15 increased the e cacy of monalizumab, even in the HLA-E low groups. ConclusionMonalizumab e cacy was correlated with HLA-E surface expression and was enhanced when NK cell activity was increased by cetuximab or cytokines. These results suggest that monalizumab may be potent against HLA-E-positive tumors and that monalizumab e cacy could be improved by promoting NK cell activity.

ECT2 promotes the occurrence and is a prognostic biomarker of head and neck squamous cell carcinoma

“…The activity of mononuclear cells may play a significant role in this process 41 . Studies indicate that B cells may participate in immune surveillance by producing antibodies, and B cells could represent a promising new direction for HNSCC therapy, allowing HNSCC patients to benefit from an immunotherapeutic perspective 42 . Research on Monalizumab primarily focuses on the treatment of solid tumors, including HNSCC.…”

Intratumoral co‐injection of NK cells and NKG2A‐neutralizing monoclonal antibodies

“…Such treatment has, thus far, shown a tolerable safety profile in humans (Andre et al , 2018 ; Tinker et al , 2019 ; Borst et al , 2020 ; Galot et al , 2021 ; Herbst et al , 2022 ). It has been demonstrated that monalizumab's efficacy strongly depends on HLA‐E expression on tumor cells (Lee et al , 2022 ). However, when used as a monotherapy, monalizumab has not shown evidence for meaningful clinical activity that, by contrast, has been substantiated when combined with durvalumab (Herbst et al , 2022 ).…”

Expresión de moléculas inmunoregulatorias en el cáncer basocelular agresivo y no agresivo y en pieles irradiadas por ultravioleta

“…Po otro lado, los melanocitos expresan en la superficie celular y secretan la molécula HLA-E (Derré et al, 2006). Aún que la expresión de la molécula HLA-G haya sido mucho estudiada en tumores espinocelulares de otras localizaciones, como cabeza y cuello (Lee et al, 2023) y en tumores ginecológics (Boujelbene et al, 2019), no hay estudios sobre HLA-E en los espinocelulares cutáneos. De la misma forma, no hay estudios sobre la molécula HLA-E en carcinomas basocelulares.…”