Abstract B41: Neutrophils modulate T-cell recruitment and promote hepatic metastases in lung cancer

Immunotherapy using checkpoint inhibitors has shown success in the treatment of late-stage non-small cell lung carcinomas (NSCLC). Indeed, nivolumab (anti-PD1 antibody) increased overall response by 9 % and overall survival by 3 months compared to chemotherapy (docetaxel). Combining Ipilimumab (anti...

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Veröffentlicht in:Cancer immunology research 2018-09, Vol.6 (9_Supplement), p.B41-B41
Hauptverfasser: Rayes, Roni F., Tinfow, Alexandra, Antonatos, Dorothy, Bourdeau, France, Giannias, Betty, Spicer, Jonathan D.
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Sprache:eng
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Zusammenfassung:Immunotherapy using checkpoint inhibitors has shown success in the treatment of late-stage non-small cell lung carcinomas (NSCLC). Indeed, nivolumab (anti-PD1 antibody) increased overall response by 9 % and overall survival by 3 months compared to chemotherapy (docetaxel). Combining Ipilimumab (anti-CTLA-4 antibody), another immune checkpoint inhibitor, with nivolumab was shown to improve response rates and survivals in NSCLC patients compared to nivolumab alone (phase 1/2 study). Despite these advances, there are still many patients that are non-responsive to available immunotherapies. We hypothesize that the immune system can overtake the inhibition of immune suppression via other mechanisms leading to a more immune suppressive tumor microenvironment. Neutrophils, being amongst the first cells of our innate immune system to be recruited to the tumor microenvironment, are key players in modulating other immune cells. Indeed, we and others have demonstrated that neutrophils play a critical role during cancer progression and from a clinical standpoint elevated neutrophil counts both in circulation and within growing lesions have been associated with poor oncologic outcomes. Therefore, neutrophil could well be the immunosuppressive switch in the tumor microenvironment. To test our hypothesis, we injected liver metastatic lung carcinoma cells into mice treated with daily injection of neutrophil elastase inhibitor (NEi, Sivelestat) and into untreated (control) mice. We then collected the livers of those mice at multiple time points post-tumor inoculation and analyzed the immune profile of these mice. As expected, NEi-treated mice had significantly less liver metastases than control mice (p < 0.05) indicating that neutrophils play a pro-tumor role in cancer progression. Furthermore, NEi-treated mice had a significant decrease in the number of tumor infiltrating granulocytes (GR1+ cells, p
ISSN:2326-6066
2326-6074
DOI:10.1158/2326-6074.TUMIMM17-B41