Genomic landscape associated with potential response to anti-CTLA-4 treatment in cancers

Chan Young Ock, Jun Eul Hwang, Bhumsuk Keam, Sang Bae Kim, Jae Jun Shim, Hee Jin Jang, Sarang Park, Bo Hwa Sohn, Minse Cha, Jaffer A. Ajani, Scott Kopetz, Keun Wook Lee, Tae Min Kim, Dae Seog Heo, Ju Seog Lee

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Immunotherapy has emerged as a promising anti-cancer treatment, however, little is known about the genetic characteristics that dictate response to immunotherapy. We develop a transcriptional predictor of immunotherapy response and assess its prediction in genomic data from ∼10,000 human tissues across 30 different cancer types to estimate the potential response to immunotherapy. The integrative analysis reveals two distinct tumor types: the mutator type is positively associated with potential response to immunotherapy, whereas the chromosome-instable type is negatively associated with it. We identify somatic mutations and copy number alterations significantly associated with potential response to immunotherapy, in particular treatment with anti-CTLA-4 antibody. Our findings suggest that tumors may evolve through two different paths that would lead to marked differences in immunotherapy response as well as different strategies for evading immune surveillance. Our analysis provides resources to facilitate the discovery of predictive biomarkers for immunotherapy that could be tested in clinical trials.

Original languageEnglish
Article number1050
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - 1 Dec 2017

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Immunotherapy
Tumors
cancer
Oncology
Biomarkers
Chromosomes
Neoplasms
Tissue
Antibodies
Therapeutics
tumors
biomarkers
chromosomes
mutations
surveillance
predictions
antibodies
resources
Clinical Trials
estimates

Cite this

Ock, Chan Young ; Hwang, Jun Eul ; Keam, Bhumsuk ; Kim, Sang Bae ; Shim, Jae Jun ; Jang, Hee Jin ; Park, Sarang ; Sohn, Bo Hwa ; Cha, Minse ; Ajani, Jaffer A. ; Kopetz, Scott ; Lee, Keun Wook ; Kim, Tae Min ; Heo, Dae Seog ; Lee, Ju Seog. / Genomic landscape associated with potential response to anti-CTLA-4 treatment in cancers. In: Nature Communications. 2017 ; Vol. 8, No. 1.
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abstract = "Immunotherapy has emerged as a promising anti-cancer treatment, however, little is known about the genetic characteristics that dictate response to immunotherapy. We develop a transcriptional predictor of immunotherapy response and assess its prediction in genomic data from ∼10,000 human tissues across 30 different cancer types to estimate the potential response to immunotherapy. The integrative analysis reveals two distinct tumor types: the mutator type is positively associated with potential response to immunotherapy, whereas the chromosome-instable type is negatively associated with it. We identify somatic mutations and copy number alterations significantly associated with potential response to immunotherapy, in particular treatment with anti-CTLA-4 antibody. Our findings suggest that tumors may evolve through two different paths that would lead to marked differences in immunotherapy response as well as different strategies for evading immune surveillance. Our analysis provides resources to facilitate the discovery of predictive biomarkers for immunotherapy that could be tested in clinical trials.",
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Ock, CY, Hwang, JE, Keam, B, Kim, SB, Shim, JJ, Jang, HJ, Park, S, Sohn, BH, Cha, M, Ajani, JA, Kopetz, S, Lee, KW, Kim, TM, Heo, DS & Lee, JS 2017, 'Genomic landscape associated with potential response to anti-CTLA-4 treatment in cancers', Nature Communications, vol. 8, no. 1, 1050. https://doi.org/10.1038/s41467-017-01018-0

Genomic landscape associated with potential response to anti-CTLA-4 treatment in cancers. / Ock, Chan Young; Hwang, Jun Eul; Keam, Bhumsuk; Kim, Sang Bae; Shim, Jae Jun; Jang, Hee Jin; Park, Sarang; Sohn, Bo Hwa; Cha, Minse; Ajani, Jaffer A.; Kopetz, Scott; Lee, Keun Wook; Kim, Tae Min; Heo, Dae Seog; Lee, Ju Seog.

In: Nature Communications, Vol. 8, No. 1, 1050, 01.12.2017.

Research output: Contribution to journalArticle

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AU - Ock, Chan Young

AU - Hwang, Jun Eul

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AU - Jang, Hee Jin

AU - Park, Sarang

AU - Sohn, Bo Hwa

AU - Cha, Minse

AU - Ajani, Jaffer A.

AU - Kopetz, Scott

AU - Lee, Keun Wook

AU - Kim, Tae Min

AU - Heo, Dae Seog

AU - Lee, Ju Seog

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