SPP1 and cancer: Cluster 3 TAMs were found in most cancer types, and partially recapitulated a gene signature that has been associated with immunotherapy resistance in melanoma68, with high expression of SPP1, RNASE1, NUPR1 and TREM2. TREM2 has been described in diverse contexts, including in the maintenance of microglial fitness in the context of Alzheimer disease69, in association with lipid-associated TAMs70, and furthermore, experimental data on mice shows that inhibition of TREM2 potentiates immunotherapy response and inhibits tumour growth71.