Cluster-derived, tumour-reactive T cells from clinical samples – Immunology Research

A high density of tumour-infiltrating lymphocytes (TILs), which is indicative of an immunologically ‘hot’ tumour, is a key predictor of improved prognosis and therapy response in various types of tumour. Furthermore, closer proximity of TILs to tumour cells in the tumour microenvironment is associated with more favourable responses to immunotherapy, consistent with the importance of direct interactions between cytotoxic TILs and tumour cells for tumour control. Ibáñez-Molero and Veldman et al. now show that such TIL-containing heterotypic cell clusters can be isolated and expanded from clinical samples, providing insight into their distinct phenotype and antitumour function.

To extend this finding to clinical cancer samples, the authors analysed 21 human melanoma metastases from anatomical sites such as lymph nodes. After brief enzymatic digestion, the samples were assessed by flow cytometry using markers for melanoma cells, CD8⁺ T cells and antigen-presenting cells (APCs). Heterotypic cell clusters — both T cell–melanoma and T cell–APC clusters — were observed in all patient samples, which was further confirmed by imaging flow cytometry and multiplex immunofluorescence analysis.