M1hot tumour associated macrophages are positively associated with tissue-resident memory T cell responses and survival outcomes in human lung cancer (bulk).

Tumour-associated macrophages (TAMs) are classified as M1 (“anti-tumour”) and M2 (“pro-tumour”), but their balance has not yet been accurately established in human cancer tissue. Here, we present bulk and single-cell transcriptomic data from human TAMs isolated from lung cancer compared with autologous non-tumour involved lung tissue macrophages (N-TAM). TAMs have a profoundly different transcriptomic profile from N-TAMs and displayed a broad M2 pro-tumour signature that was homogeneous across all the lung cancer patients studied. However, in some tumours, we found TAM populations that simultaneously displayed strong M1 gene expression pattern. These M1hot TAMs appeared to contribute to effective anti-tumour immunity via expression of T cell chemo-attractants (CXCL9, 10 and 11). We found that M1hot TAMs expressed low levels of FABP3, 4 and 5, take up less fatty acids and showed “metabolic generosity” to tissue resident memory T cells (TRM) by allowing them access to this essential nutrient resource that is required for their maintenance. Importantly, tumours harbouring M1hot TAMs were highly enriched for TRM cells and were also associated with improved overall survival outcomes. Our findings suggest that immunotherapeutic approaches aimed at inducing the expression of M1hot program in TAMs rather than generically eliminating all TAMs are likely to be beneficial. mRNA profiles of Tumour Associated Macrophages isolated from human lung cancer and macrophages from paired lung were generated by deep sequencing, using Illumina HiSeq 2500.