Adoptive transfer of tumour infiltrating lymphocytes (TIL therapy) has shown high efficacy in a phase III trial for melanoma patients (M14TIL), and in phase I trials for other solid cancers. However, not all patients respond to TIL therapy. Good prediction tools would help to select which patients may benefit most. The tumour microenvironment is infiltrated by different types of lymphoid and myeloid cells, which communicate with each other. We therefore hypothesized that the presence of specific immune cell types may explain the variation in TIL products.
To define tumour-specific alterations of immune infiltrates, we characterized the myeloid and lymphoid cell populations present in tumour lesions and healthy adjacent tissue from 26 early-stage NSCLC patients by flow cytometry. We generated TIL products according to the clinical expansion protocol and determined their tumour reactivity based on cytokine production upon co-culture with the autologous tumour digest. Polyfunctional T cells were defined as cells producing at least two cytokines. Data were analysed using Cytotree, a R/Bioconductor package to analyse flow data in an unbiased fashion. Spearman’s Rank Correlation was used to correlate immune infiltrates with expansion rate and percentage of polyfunctional T cell.
The majority of immune cells in the tumour tissue consisted of lymphoid cells (T cells 67%; B cells 16%; NK(T) cells 3.5%), which were all increased compared to the healthy adjacent tissue (T cells 33.6%; B cells 2.6%; NK(T) cells 13%). This increase was at cost of monocyte and dendritic cell infiltrates, which were decreased in tumour tissue (9%) compared to the healthy adjacent tissue (18%). None of the immune infiltrates correlated with the expansion rate of TILs. Monocytes, dendritic cell and NK cell infiltrates showed a negative association with the percentage of polyfunctional T cells. Interestingly, the presence of B cells was positively associated with the percentage of polyfunctional T cells.
We found that specific immune infiltrates in the tumour tissue associate with the functionality of TIL products, which may help select for TIL products with highly responsive T cells against NSCLC tumours.
The authors.
Sanquin.
J.B.A.G. Haanen: Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, Achilles Therapeutics, Ipsen, Merck Sharpe & Dohme, Merck Serono, Pfizer, Molecular Partners, Novartis, Roche, Sanofi, Third Rock Venture, Iovance Biotherapeutics; Financial Interests, Institutional, Advisory Board, SAB member: BioNTech, Immunocore, Gadeta, Instil Bio, PokeAcel, T-Knife; Financial Interests, Personal, Advisory Board, SAB member: Neogene Therapeutics, Scenic; Financial Interests, Personal, Stocks/Shares: Neogene Therapeutics; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, BioNTech US, Merck Sharpe & Dohme, Amgen, Novartis, Asher Bio; Non-Financial Interests, Personal, Member: ASCO, AACR, SITC; Other, Personal, Other, Editorial Board ESMO Open: ESMO; Other, Personal, Other, Editor-in-Chief IOTECH: ESMO; Other, Personal, Other, Editorial Board: Kidney Cancer. All other authors have declared no conflicts of interest.