Expression of scavenger receptor MARCO defines a targetable tumor-associated macrophage subset in non-small cell lung cancer.
Tumor-associated macrophages (TAMs) are attractive targets for immunotherapy. Recently, studies in animal models showed that treatment with an anti-TAM antibody directed against the scavenger receptor MARCO resulted in suppression of tumor growth and metastatic dissemination. Here we investigated the expression of MARCO in relation to other macrophage markers and immune pathways in a non-small cell lung cancer (NSCLC) cohort (n = 352). MARCO, CD68, CD163, MSR1 and programmed death ligand-1 (PD-L1) were analyzed by immunohistochemistry and immunofluorescence, and associations to other immune cells and regulatory pathways were studied in a subset of cases (n = 199) with available RNA-seq data. We observed a large variation in macrophage density between cases and a strong correlation between CD68 and CD163, suggesting that the majority of TAMs present in NSCLC exhibit a protumor phenotype. Correlation to clinical data only showed a weak trend toward worse survival for patients with high macrophage infiltration. Interestingly, MARCO was expressed on a distinct subpopulation of TAMs, which tended to aggregate in close proximity to tumor cell nests. On the transcriptomic level, we found a positive association between MARCO gene expression and general immune response pathways including strong links to immunosuppressive TAMs, T-cell infiltration and immune checkpoint molecules. Indeed, a higher macrophage infiltration was seen in tumors expressing PD-L1, and macrophages residing within tumor cell nests co-expressed MARCO and PD-L1. Thus, MARCO is a potential new immune target for anti-TAM treatment in a subset of NSCLC patients, possibly in combination with available immune checkpoint inhibitors.
['La Fleur|Linnéa|L|0000-0001-5638-9818', 'Boura|Vanessa F|VF|', 'Alexeyenko|Andrey|A|', 'Berglund|Anders|A|', 'Pontén|Victor|V|', 'Mattsson|Johanna S M|JSM|', 'Djureinovic|Dijana|D|', 'Persson|Johan|J|', 'Brunnström|Hans|H|', 'Isaksson|Johan|J|', 'Brandén|Eva|E|', 'Koyi|Hirsh|H|', 'Micke|Patrick|P|', 'Karlsson|Mikael C I|MCI|', 'Botling|Johan|J|']
D000230:Adenocarcinoma D000368:Aged D014408:Biomarkers, Tumor D018287:Carcinoma, Large Cell D002289:Carcinoma, Non-Small-Cell Lung D002294:Carcinoma, Squamous Cell D015331:Cohort Studies D005260:Female D005500:Follow-Up Studies D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008175:Lung Neoplasms D008264:Macrophages D008297:Male D011379:Prognosis D011971:Receptors, Immunologic D015996:Survival Rate D059016:Tumor Microenvironment
MARCO tumor-associated macrophages lung cancer PD-L1 immune therapy