PT  - JOURNAL ARTICLE
AU  - Paola Marie Marcovecchio
AU  - Graham Thomas
AU  - Shahram Salek-Ardakani
TI  - CXCL9-expressing tumor-associated macrophages: new players in the fight against cancer
AID  - 10.1136/jitc-2020-002045
DP  - 2021 Feb 01
TA  - Journal for ImmunoTherapy of Cancer
PG  - e002045
VI  - 9
IP  - 2
4099  - http://jitc.bmj.com/content/9/2/e002045.short
4100  - http://jitc.bmj.com/content/9/2/e002045.full
SO  - J Immunother Cancer2021 Feb 01; 9
AB  - Tumor-associated macrophages (TAMs) are among the main contributors to immune suppression in the tumor microenvironment, however, TAM depletion strategies have yielded little clinical benefit. Here, we discuss the concept that TAMs are also key regulators of anti-PD(L)-1-mediated CD8 T cell-dependent immunity. Emerging data suggest that expression of the chemokine CXCL9 by TAMs regulates the recruitment and positioning of CXCR3-expressing stem-like CD8 T (Tstem) cells that underlie clinical responses to anti-PD(L)-1 treatment. We evaluate clinical and mechanistic studies that establish relationships between CXCL9-expressing TAMs, Tstem and antitumor immunity. Therapies that enhance anti-PD(L)-1 response rates must consider TAM CXCL9 expression. In this perspective, we discuss opportunities to enhance the frequency and function of CXCL9 expressing TAMs and draw on comparative analyzes from infectious disease models to highlight potential functions of these cells beyond Tstem recruitment.