I am establishing a Tcell co-cultured 3D human cancer spheroid model. 1 hour after addition of HLA-matched Tcells to spheroids, I see that the Tcells infiltrate the spheroids. I used this model to check if immunotherapy using anti-PD1 inhibitor is a viable option to treat this cancer. On performing cyrotoxicity assay, I found that Tcells alone was killing the cancer cells and the addition of anti-PD1 checkpoint inhibitor actually suppressed the cytotoxicity. I wonder if the Tcells were compatible with the cancer cells even though they were HLA matched. what additional test should be done to confirm that. What could be the other possible reasons for the observed cytotoxicity?
If you're working with cell lines, you cannot say that T cells are HLA-matched right? by HLA matched, you should mean that the tumor and T cells are from the same donor. Is there only CD8+ T cells in your test or whole T cells with NK cells as well? a minor mismatch can still induce MLR especially if your tumor is heavily mutated which is most likely going to be the case with cell lines. Maybe you could add anti-classI mAb in your culture to see if cytotoxicity is due to alloreactivity
Thanks for ur answer and suggestion. Immunology is relatively new for me. I am not working with cell lines. My 3D cultures are from patient derived xenografts (PDX). The Tcells are not from the same donor as the PDX, but they are hla matched. There are only CD8+ and CD4+ Tcells and no DCs or NK cells in the mix.
Hi, I support Giles that you can anti class1mAb in your culture to check if the cytotoxicity is by alloreactions.
The HLA test is a powerful test
, but the mixture of cytokines and the T cells is also powerful. Cytokines on their own do finish off any anomalies for their own. There are more tests. Any compatibility test for organs. "IHC (Histocompatibility complex)..."
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