Figure S6: The bar graphs above show the FACS analysis of ICOS expression (%) at Day 2 and Day 8 measured on CD4 and CD8 T cells from TDLN. On Day 2, anti PD-1 treated mice showed upregulation of ICOS in CD4 and CD8 T cells, compared to that of PBS group (~ 2-fold in CD4 T cells and 2.5-fold in CD8 T cells). On Day 8, ICOS levels on both CD4+ and CD8+ T cells decreased in the anti PD-1 treatment group, relative to that of Day 2, and PBS group remained similar with Day 2. (*: P<0.05, **: P<0.01, the data was presented as mean {plus minus} SD, n=5)
ARTICLE ABSTRACT
Immunotherapy is innovating clinical cancer management. Nevertheless, only a small fraction of patient's benefit from current immunotherapies. To improve clinical management of cancer immunotherapy, it is critical to develop strategies for response monitoring and prediction. In this study, we describe inducible T-cell costimulator (ICOS) as a conserved mediator of immune response across multiple therapy strategies. ICOS expression was evaluated by flow cytometry, 89Zr-DFO-ICOS mAb PET/CT imaging was performed on Lewis lung cancer models treated with different immunotherapy strategies, and the change in tumor volume was used as a read-out for therapeutic response. ImmunoPET imaging of ICOS enabled sensitive and specific detection of activated T cells and early benchmarking of immune response. A STING (stimulator of interferon genes) agonist was identified as a promising therapeutic approach in this manner. The STING agonist generated significantly stronger immune responses as measured by ICOS ImmunoPET and delayed tumor growth compared with programmed death-1 checkpoint blockade. More importantly, ICOS ImmunoPET enabled early and robust prediction of therapeutic response across multiple treatment regimens. These data show that ICOS is an indicator of T-cell–mediated immune response and suggests ICOS ImmunoPET as a promising strategy for monitoring, comparing, and predicting immunotherapy success in cancer.
ICOS ImmunoPET is a promising strategy to noninvasively predict and monitor immunotherapy response.See related commentary by Choyke, p. 2975
