TREM2 macrophages are associated with enhanced response to PD-1 blockade in human hepatocellular carcinoma
Hamon, P.; Park, M. D.; Le Berichel, J.; Cohen, M.; Soong, B. Y.; Buckup, M.; Hennequin, C.; Lindblad, K. E.; Mattiuz, R.; Figueiredo, I.; Tabachnikova, A.; Dawson, T.; D'souza, D.; Troncoso, L.; Ioannou, G.; Price, C.; Fernandez, N.; Giladi, A.; Barboy, O.; Zhao, Z.; Ozbey, S.; Cappuyns, S.; Reid, A.; Hamel, S.; Kim, J.; Donne, R.; Chang, C.; Marvin, R.; Stefanos, H.; Chung, G.; Merand, R.; Halasz, L.; Hegde, S.; Guerin, L. M.; Ni, M.; Wei, Y.; Atwal, G.; Lansky, A.; Jamal, H.; Yi, N.; Chin, T.; James, N.; Malissen, N.; Desland, F.; Lavin, Y.; Ward, S. C.; Fiel, M. I.; Brody, R.; Dekervel, J.
Show abstract
Macrophages are known to dampen tumor immunity. However, identifying druggable targets that modulate these cells to improve existing immunotherapies has been limited by a dearth of studies identifying macrophages that associate with pathological response to immune checkpoint blockade. To fulfill this unmet clinical need, we leveraged transcriptional and spatial profiling of specimens collected from a Phase II clinical trial studying neoadjuvant PD-1 blockade in patients with hepatocellular carcinoma (HCC). We determined that the intratumoral abundance of TREM2-expressing macrophages and serological levels of soluble TREM2 are elevated in patients who responded to PD-1 blockade, compared to non-responders. We validated these findings in a second HCC cohort and in the IMbrave150 trial. These highlight the robust potential for TREM2 macrophages to predict therapeutic responses of HCC to immunotherapy. Therefore, our study provides a novel basis for the use of TREM2 macrophages to strategize treatment for patients with HCC to maximize therapeutic benefit.
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