Immune control of hepatocellular carcinoma: TCR-agnostic differentiation of tumor-specific CD8 T cells

Background and Aims CD8 T cells play a critical role in limiting tumor progression and in tumor response to immune checkpoint inhibition (CPI). However, assessment of patient-specific T cell responses directed against tumors is still challenging and not feasible in clinical settings. This significantly impedes downstream evaluation of individual immune control and the functional evaluation of tumor-specific immune responses. In our preliminary work, we established a method to detect tumor-associated CD8 T cells.

Method In an immune profiling we compared PBMCs derived from a CPI-responding cancer patient with a healthy donor. Specifically, we used flow cytometry for analyisis of expression patterns on the cellular surface of CD8 T cells. An antibody panel comprising 360 specificities was used for staining and subsequent profiling of corresponding samples. With this approach, we found a promising marker combination that identifies a CD8 T cell subset that is predominantly found in cancer patients and absent in healthy individuals. We used statistical analysis as well as different molecular approaches to validate the results in a HCC patient cohort.

Results The expression of CD11a and CD82 on CD8 T cells differentiate naive, pathogen-specific, and tumor-associated subsets. CD11a^loCD82^lo expression constitute naive CD8 T cells. CD11a^hiCD82^lo expression identifies pathogen-specific T cells, and CD11a^intCD82^hi expression reveals tumor-associated T cells. In healthy controls we found tumor-specific T cells elevated in one out of 65 (<2%). In contrast, cancer patients (mostly HCC patients) without immunotherapeutic treatment at the time of analysis showed elevated levels of tumor-specific T cells in 34 out of 37 cases (92%). Furthermore, we observed in HCC patients undergoing immunotherapies a correlation between therapy response and the frequencies of tumor-specific T cells.

Conclusion We found a promising biomarker combination for CD8 T cells that could be relevant for the rapid and simple detection of tumor-specific T cell subsets. These findings may be important for clinical diagnostics and therapeutic interventions in patient-specific approaches.

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Publication History

Article published online:
19 August 2022