Hogan, et al. – Summary

Hogan SA, Courtier A, Cheng PF, Jaberg-Bentele NF, Goldinger SM, Manuel M, Perez S, Plantier N, Mouret JF, Nguyen-Kim TDL, Raaijmakers MIG, Kvistborg P, Pasqual N, Haanen JBAG, Dummer R, Levesque MP. Peripheral blood TCR repertoire profiling may facilitate patient stratification for immunotherapy against melanoma. Cancer Immunol Res. 2019; 7(1):77-85. Available at: https://cancerimmunolres.aacrjournals.org/content/7/1/77

Immunotherapies have proven very effective in treating some metastatic melanoma patients. However, clinicians are still lacking tools allowing to predict which patient will most benefit from those treatment. In this study, we showed that by analysing some white blood cells (T cells) from the patient before the treatment begins, we can make an accurately anticipate his response either of the two immunotherapies currently approved (anti-PD1 or anti-CTLA4).

T cells are a particular set of white blood cells which are trained to recognise and kill malignant cells and thus fight against tumours.

The analysis of the whole pool of T cell present in an individual, informs on its ability to fight against foreign particles. Nevertheless, the presence of tumour-recognising T cell does not guarantee a proper immune response, those cells may still be hindered in their function by other mechanisms. Those prevention mechanisms are the ones being targeted by the immunotherapies.

The test consists in analysing the variety of T cells present in the blood of the patient, using a simple technique which can be easily applied in clinics. Although those results still have to be confirmed in a larger group, we showed that, the overall state of the T-cell pool can inform on the eventual response to anti-CTLA4 and anti-PD1 before treatment initiation.

3D representation of two different T-cell pools. Each spike represent a particular set of T cells, recognising a specific molecule. The height is the frequency of occurrence. A) This graph correspond to a very clonal repertoire, where some specialised T cells make up the majority of the repertoire. B) Represents a very homogenous repertoire, composed of equivalent frequencies of each type of T cells.

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