Malignancy increases sepsis incidence 10-fold and elevates sepsis-associated mortality. Advances in treatment have improved survival of cancer patients shortly after sepsis, but there is a paucity of information on how sepsis impacts cancer growth, development, and prognosis. To test this, cecal ligation and puncture surgery was performed on B16 melanoma-bearing mice to show that sepsis has detrimental effects in hosts with advanced tumors, leading to increased mortality. Surprisingly, mice experiencing cecal ligation and puncture–induced sepsis earlier during tumor development exhibited CD8 T cell–dependent attenuation of tumor growth. Sepsis-resistant CD8 tumor-infiltrating T cells showed increased in vivo activation, effector IFN-g cytokine production, proliferation, and expression of activation/inhibitory PD-1/LAG-3 receptors because of a sepsis-induced liberation of tumor Ags. Sepsis-reinvigorated CD8 tumor-infiltrating T cells were also amenable to (anti–PD-L1/LAG-3) checkpoint blockade therapy, further prolonging cancer-associated survival in sepsis survivors. Thus, sepsis has the capacity to improve tumor-specific CD8 T cell responses, leading to better cancer prognosis and increased survival.
Bibliographical noteFunding Information:
This work was supported by National Institutes of Health Grants GM113961 and P30CA08682 (to V.P.B.), GM115462 (to T.S.G.), T32AI007485 (to D.B.D. and I.J.J.), and T32AI007511 (to I.J.J.), The Holden Comprehensive Cancer Center and its National Cancer Institute Award P30CA086862 (to V.P.B.), and Veterans Affairs Merit Award I01BX001324 (to T.S.G.).
Copyright © 2019 by The American Association of Immunologists, Inc.
Copyright 2019 Elsevier B.V., All rights reserved.