@article{377e23b2236b46d5bd01f0d9133fad20,
title = "Distinct clinical patterns and immune infiltrates are observed at time of progression on targeted therapy versus immune checkpoint blockade for melanoma",
abstract = "ABSTRACT: We have made major advances in the treatment of melanoma through the use of targeted therapy and immune checkpoint blockade; however, clinicians are posed with therapeutic dilemmas regarding timing and sequence of therapy. There is a growing appreciation of the impact of antitumor immune responses to these therapies, and we performed studies to test the hypothesis that clinical patterns and immune infiltrates differ at progression on these treatments. We observed rapid clinical progression kinetics in patients on targeted therapy compared to immune checkpoint blockade. To gain insight into possible immune mechanisms behind these differences, we performed deep immune profiling in tumors of patients on therapy. We demonstrated low CD8+T-cell infiltrate on targeted therapy and high CD8+T-cell infiltrate on immune checkpoint blockade at clinical progression. These data have important implications, and suggest that antitumor immune responses should be assessed when considering therapeutic options for patients with melanoma.",
keywords = "BRAF, CTLA-4, Immune checkpoint blockade, PD-1, melanoma, targeted therapy",
author = "Cooper, {Zachary A.} and Alexandre Reuben and Spencer, {Christine N.} and Prieto, {Peter A.} and Austin-Breneman, {Jacob L.} and Hong Jiang and Cara Haymaker and Vancheswaran Gopalakrishnan and Tetzlaff, {Michael T.} and Frederick, {Dennie T.} and Sullivan, {Ryan J.} and Amaria, {Rodabe N.} and Patel, {Sapna P.} and Patrick Hwu and Woodman, {Scott E.} and Glitza, {Isabella C.} and Adi Diab and Vence, {Luis M.} and Jaime Rodriguez-Canales and Parra, {Edwin R.} and Wistuba, {Ignacio I.} and Coussens, {Lisa M.} and Sharpe, {Arlene H.} and Flaherty, {Keith T.} and Gershenwald, {Jeffrey E.} and Lynda Chin and Davies, {Michael A.} and Karen Clise-Dwyer and Allison, {James P.} and Padmanee Sharma and Wargo, {Jennifer A.}",
note = "Funding Information: JAW acknowledges National Institutes of Health (NIH) grants 1K08CA160692-01A1, the Melanoma Research Alliance Team Science Award, the Kenedy Memorial Foundation grant # 0727030 and the generous philanthropic support of several families whose lives have been affected by melanoma. ZAC, JAW, KTF, AHS, LMC acknowledges NIH grants U54CA163125 and U54CA163123. Supported by the philanthropic contributions to The University of Texas MD Anderson Cancer Center Melanoma Moon Shots Program. KCD, ZAC, and JAW acknowledge the support of the MD Anderson South Campus Flow Core Facility which is supported by NIH grant P30CA16672. PAP is supported by NIH grant T32 CA009599 Publisher Copyright: {\textcopyright} 2016 The Author(s). Published with license by Taylor & Francis Group, LLC.",
year = "2016",
month = mar,
day = "3",
doi = "10.1080/2162402X.2015.1136044",
language = "English (US)",
volume = "5",
journal = "OncoImmunology",
issn = "2162-4011",
publisher = "Landes Bioscience",
number = "3",
}