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Mosca, Laura; de Angelis, Alessandra; Ronchi, Andrea; De Chiara, Annarosaria; Fazioli, Flavio; Ruosi, Carlo; Altucci, Lucia; Conte, Mariarosaria; de Nigris, Filomena
Cancers, 07/2022, Letnik: 14, Številka: 14Journal Article
The major histocompatibility complex (MHC) class I expression in cancer cells has a crucial impact on the outcome of T cell-mediated cancer immunotherapy. We now determined the HLA class I allelic variants and their expression in PD-L1-deficient and positive rare sarcoma tissues. Tumor tissues were HLA-I classified based on HLA-A and -B alleles, and for class II, the HLA-DR-B by Taqman genomic PCRs. The HLA-A24*:10-B73*:01 haplotype was the most common. A general down-regulation or deletion of HLA-B mRNA and HLA-A was observed, compared to HLA-DR-B. HLA-I was almost too low to be detectable by immunohistochemistry and 32% of grade III cases were positive to PD-L1. Functional cytotoxic assays co-culturing patient biopsies with autologous T cells were used to assess their ability to kill matched tumor cells. These results establish that deletion of HLA-I loci together with their down-regulation in individual patient restrict the autologous lymphocyte cytotoxic activity, even in the presence of the immune checkpoint blocking antibody, Nivolumab. Additionally, the proposed cytotoxic test suggests a strategy to assess the sensitivity of tumor cells to T cell-mediated attack at the level of the individual patient.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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