T H 17 cells play important yet complex roles in cancer development and progression. We previously reported that T H 17 cells and IL-17 mediate resistance to anti-VEGF therapy by inducing recruitment of immunosuppressive and proangiogenic myeloid cells to the tumor microenvironment. Here, we demonstrate that IL-22, a key effector cytokine expressed by T H 17 cells, directly acts on endothelial cells to promote tumor angiogenesis. IL-22 induces endothelial cell proliferation, survival, and chemotaxis in vitro and neovascularization in an ex vivo mouse choroid explant model. Blockade of IL-22, with a neutralizing antibody, significantly inhibits tumor growth associated with reduced microvascular density. No synergistic effect of IL-22 with VEGF was observed. These results identify IL-22 as a potential therapeutic target for blocking tumor angiogenesis.
OBJECTIVE To provide continued follow-up of a cohort of ophthalmology clinician-scientists who received National Institutes of Health (NIH) K career development grants. DESIGN, SETTING, AND PARTICIPANTS Cohort study from an electronic database review of ophthalmologists who have received either a K08 or K23 career development grant from the NIH. Data were analyzed between December 30, 2015, and December 30, 2017. MAIN OUTCOMES AND MEASURES Receipt of an NIH R01 grant. RESULTS We previously characterized a group of more than 100 ophthalmologists who received K awards from 1996 to 2010, of whom 29 were awarded R01 grants. In follow-up of this cohort in 2017, 27 additional K awardees of this initial cohort were awarded an R01 from 2011 to 2017, leading to a total of 62 of 128 ophthalmologists receiving an R01. The mean time to receiving an R01 grant after the K award ended was 2.8 years. The data did not identify a definitive association with sex, having a PhD degree, or research tier of university in obtaining an R01 grant in this cohort. CONCLUSIONS AND RELEVANCE In comparison with our previous report of the same cohort, there was a 93% increase in the number of K awardees who have received an R01 award, with the mean time to award being nearly 3 years after completing their K grant. This suggests that most K awardees in ophthalmology are successful in obtaining R01 grants, but one should recognize this may be several years after their K grant has ended.
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