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Publication
Paradoxical effects of obesity on T cell function during tumor progression and
PD-1 checkpoint blockade.
Authors Wang Z, Aguilar EG, Luna JI, Dunai C, Khuat LT, Le CT, Mirsoian A, Minnar CM,
Stoffel KM, Sturgill IR, Grossenbacher SK, Withers SS, Rebhun RB,
Hartigan-O'Connor DJ, Méndez-Lagares G, Tarantal AF, Isseroff RR, Griffith TS,
Schalper KA, Merleev A, Saha A, Maverakis E, Kelly K, Aljumaily R, Ibrahimi S,
Mukherjee S, Machiorlatti M, Vesely SK, Longo DL, Blazar BR, Canter RJ, Murphy
WJ, Monjazeb AM
Submitted By Submitted Externally on 5/21/2019
Status Published
Journal Nature medicine
Year 2019
Date Published 1/1/2019
Volume : Pages 25 : 141 - 151
PubMed Reference 30420753
Abstract The recent successes of immunotherapy have shifted the paradigm in cancer
treatment, but because only a percentage of patients are responsive to
immunotherapy, it is imperative to identify factors impacting outcome. Obesity
is reaching pandemic proportions and is a major risk factor for certain
malignancies, but the impact of obesity on immune responses, in general and in
cancer immunotherapy, is poorly understood. Here, we demonstrate, across
multiple species and tumor models, that obesity results in increased immune
aging, tumor progression and PD-1-mediated T cell dysfunction which is driven,
at least in part, by leptin. However, obesity is also associated with increased
efficacy of PD-1/PD-L1 blockade in both tumor-bearing mice and clinical cancer
patients. These findings advance our understanding of obesity-induced immune
dysfunction and its consequences in cancer and highlight obesity as a biomarker
for some cancer immunotherapies. These data indicate a paradoxical impact of
obesity on cancer. There is heightened immune dysfunction and tumor progression
but also greater anti-tumor efficacy and survival after checkpoint blockade
which directly targets some of the pathways activated in obesity.





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