TY - JOUR
T1 - Genomic and immune heterogeneity are associated with differential responses to therapy in melanoma
AU - Reuben, Alexandre
AU - Spencer, Christine N.
AU - Prieto, Peter A.
AU - Gopalakrishnan, Vancheswaran
AU - Reddy, Sangeetha M.
AU - Miller, John P.
AU - Mao, Xizeng
AU - De Macedo, Mariana Petaccia
AU - Chen, Jiong
AU - Song, Xingzhi
AU - Jiang, Hong
AU - Chen, Pei Ling
AU - Beird, Hannah C.
AU - Garber, Haven R.
AU - Roh, Whijae
AU - Wani, Khalida
AU - Chen, Eveline
AU - Haymaker, Cara
AU - Forget, Marie Andrée
AU - Little, Latasha D.
AU - Gumbs, Curtis
AU - Thornton, Rebecca L.
AU - Hudgens, Courtney W.
AU - Chen, Wei Shen
AU - Austin-Breneman, Jacob
AU - Sloane, Robert Szczepaniak
AU - Nezi, Luigi
AU - Cogdill, Alexandria P.
AU - Bernatchez, Chantale
AU - Roszik, Jason
AU - Hwu, Patrick
AU - Woodman, Scott E.
AU - Chin, Lynda
AU - Tawbi, Hussein
AU - Davies, Michael A.
AU - Gershenwald, Jeffrey E.
AU - Amaria, Rodabe N.
AU - Glitza, Isabella C.
AU - Diab, Adi
AU - Patel, Sapna P.
AU - Hu, Jianhua
AU - Lee, Jeffrey E.
AU - Grimm, Elizabeth A.
AU - Tetzlaff, Michael T.
AU - Lazar, Alexander J.
AU - Wistuba, Ignacio I.
AU - Clise-Dwyer, Karen
AU - Carter, Brett W.
AU - Zhang, Jianhua
AU - Futreal, P. Andrew
AU - Sharma, Padmanee
AU - Allison, James P.
AU - Cooper, Zachary A.
AU - Wargo, Jennifer A.
N1 - Funding Information:
A.R. is supported by the Kimberley Clarke Foundation Award for Scientific Achievement awarded by the University of Texas MD Anderson Cancer Center’s Odyssey Fellowship Program. J.A.W. acknowledges 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. This work was supported by National Institutes of Health grants 1K08CA160692-01A1 (J.A.W.), U54CA163125 (Z.A.C., J.A.W., and L.C.), T32CA009599 (P.A.P.), and 5T32CA163185 (P.L.C.). J.P.A., P.S., and J.A.W. are members of the Parker Institute for Cancer Immunotherapy at MD Anderson Cancer Center. W.R. is supported by the CPRIT Graduate Scholar Award. L.C. is a CPRIT Scholar in Cancer Research and was supported by a grant from the Cancer Prevention Research Institute of Texas (R1204). P.A.F. holds CPRIT funding (R1205 01) and a Robert Welch Distinguished University Chair (G-0040). This work was supported by MD Anderson’s Institutional Tissue Bank Award (2P30CA016672) from the National Cancer Institute. This study was also supported by philanthropic contributions to The University of Texas MD Anderson Cancer Center Melanoma Moon Shot Program. The National Cancer Institute SPORE grant P50 CA093459, and philanthropic contributions to The University of Texas MD Anderson Cancer Center Moon Shots Program, The University of Texas MD Anderson Cancer Center Various Donors Melanoma and Skin Cancers Priority Program Fund, the Miriam and Jim Mulva Research Fund, the McCarthy Skin Cancer Research Fund, and the Marit Peterson Fund for Melanoma Research. This work used services of MDACC Support Grant P30 CA16672-supported core labs including the South Campus Flow Cytometry and Cell Sorting Core Laboratory.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Appreciation for genomic and immune heterogeneity in cancer has grown though the relationship of these factors to treatment response has not been thoroughly elucidated. To better understand this, we studied a large cohort of melanoma patients treated with targeted therapy or immune checkpoint blockade (n = 60). Heterogeneity in therapeutic responses via radiologic assessment was observed in the majority of patients. Synchronous melanoma metastases were analyzed via deep genomic and immune profiling, and revealed substantial genomic and immune heterogeneity in all patients studied, with considerable diversity in T cell frequency, and few shared T cell clones (<8% on average) across the cohort. Variables related to treatment response were identified via these approaches and through novel radiomic assessment. These data yield insight into differential therapeutic responses to targeted therapy and immune checkpoint blockade in melanoma, and have key translational implications in the age of precision medicine.
AB - Appreciation for genomic and immune heterogeneity in cancer has grown though the relationship of these factors to treatment response has not been thoroughly elucidated. To better understand this, we studied a large cohort of melanoma patients treated with targeted therapy or immune checkpoint blockade (n = 60). Heterogeneity in therapeutic responses via radiologic assessment was observed in the majority of patients. Synchronous melanoma metastases were analyzed via deep genomic and immune profiling, and revealed substantial genomic and immune heterogeneity in all patients studied, with considerable diversity in T cell frequency, and few shared T cell clones (<8% on average) across the cohort. Variables related to treatment response were identified via these approaches and through novel radiomic assessment. These data yield insight into differential therapeutic responses to targeted therapy and immune checkpoint blockade in melanoma, and have key translational implications in the age of precision medicine.
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U2 - 10.1038/s41525-017-0013-8
DO - 10.1038/s41525-017-0013-8
M3 - Article
C2 - 28819565
AN - SCOPUS:85028422302
SN - 2056-7944
VL - 2
JO - npj Genomic Medicine
JF - npj Genomic Medicine
IS - 1
M1 - 10
ER -