Evaluating the impact of age on immune checkpoint therapy biomarkers

Rossin Erbe; Zheyu Wang; Sharon Wu; Joanne Xiu; Neeha Zaidi; Jennifer La; David Tuck; Nathanael Fillmore; Nicolas A. Giraldo; Michael Topper; Stephen Baylin; Marc Lippman; Claudine Isaacs; Reva Basho; Ilya Serebriiskii; Heinz Josef Lenz; Igor Astsaturov; John Marshall; Josephine Taverna; Jerry Lee; Elizabeth M. Jaffee; Evanthia T. Roussos Torres; Ashani Weeraratna; Hariharan Easwaran; Elana J. Fertig

doi:10.1016/j.celrep.2021.109599

Evaluating the impact of age on immune checkpoint therapy biomarkers

Rossin Erbe, Zheyu Wang, Sharon Wu, Joanne Xiu, Neeha Zaidi, Jennifer La, David Tuck, Nathanael Fillmore, Nicolas A. Giraldo, Michael Topper, Stephen Baylin, Marc Lippman, Claudine Isaacs, Reva Basho, Ilya Serebriiskii, Heinz Josef Lenz, Igor Astsaturov, John Marshall, Josephine Taverna, Jerry LeeElizabeth M. Jaffee, Evanthia T. Roussos Torres, Ashani Weeraratna, Hariharan Easwaran, Elana J. Fertig

Research output: Contribution to journal › Article › peer-review

Abstract

Both tumors and aging alter the immune landscape of tissues. These interactions may play an important role in tumor progression among elderly patients and may suggest considerations for patient care. We leverage large-scale genomic and clinical databases to perform comprehensive comparative analysis of molecular and cellular markers of immune checkpoint blockade (ICB) response with patient age. These analyses demonstrate that aging is associated with increased tumor mutational burden, increased expression and decreased promoter methylation of immune checkpoint genes, and increased interferon gamma signaling in older patients in many cancer types studied, all of which are expected to promote ICB efficacy. Concurrently, we observe age-related alterations that might be expected to reduce ICB efficacy, such as decreases in T cell receptor diversity. Altogether, these changes suggest the capacity for robust ICB response in many older patients, which may warrant large-scale prospective study on ICB therapies among patients of advanced age.

Original language	English (US)
Article number	109599
Journal	Cell Reports
Volume	36
Issue number	8
DOIs	https://doi.org/10.1016/j.celrep.2021.109599
State	Published - Aug 24 2021

Keywords

TCGA
aging
cancer
genomics
immune
immunotherapy

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2021.109599

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Erbe, R., Wang, Z., Wu, S., Xiu, J., Zaidi, N., La, J., Tuck, D., Fillmore, N., Giraldo, N. A., Topper, M., Baylin, S., Lippman, M., Isaacs, C., Basho, R., Serebriiskii, I., Lenz, H. J., Astsaturov, I., Marshall, J., Taverna, J., ... Fertig, E. J. (2021). Evaluating the impact of age on immune checkpoint therapy biomarkers. Cell Reports, 36(8), Article 109599. https://doi.org/10.1016/j.celrep.2021.109599

Erbe, R, Wang, Z, Wu, S, Xiu, J, Zaidi, N, La, J, Tuck, D, Fillmore, N, Giraldo, NA, Topper, M , Baylin, S, Lippman, M, Isaacs, C, Basho, R, Serebriiskii, I, Lenz, HJ, Astsaturov, I, Marshall, J, Taverna, J, Lee, J, Jaffee, EM, Roussos Torres, ET, Weeraratna, A , Easwaran, H & Fertig, EJ 2021, 'Evaluating the impact of age on immune checkpoint therapy biomarkers', Cell Reports, vol. 36, no. 8, 109599. https://doi.org/10.1016/j.celrep.2021.109599

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title = "Evaluating the impact of age on immune checkpoint therapy biomarkers",

abstract = "Both tumors and aging alter the immune landscape of tissues. These interactions may play an important role in tumor progression among elderly patients and may suggest considerations for patient care. We leverage large-scale genomic and clinical databases to perform comprehensive comparative analysis of molecular and cellular markers of immune checkpoint blockade (ICB) response with patient age. These analyses demonstrate that aging is associated with increased tumor mutational burden, increased expression and decreased promoter methylation of immune checkpoint genes, and increased interferon gamma signaling in older patients in many cancer types studied, all of which are expected to promote ICB efficacy. Concurrently, we observe age-related alterations that might be expected to reduce ICB efficacy, such as decreases in T cell receptor diversity. Altogether, these changes suggest the capacity for robust ICB response in many older patients, which may warrant large-scale prospective study on ICB therapies among patients of advanced age.",

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author = "Rossin Erbe and Zheyu Wang and Sharon Wu and Joanne Xiu and Neeha Zaidi and Jennifer La and David Tuck and Nathanael Fillmore and Giraldo, {Nicolas A.} and Michael Topper and Stephen Baylin and Marc Lippman and Claudine Isaacs and Reva Basho and Ilya Serebriiskii and Lenz, {Heinz Josef} and Igor Astsaturov and John Marshall and Josephine Taverna and Jerry Lee and Jaffee, {Elizabeth M.} and {Roussos Torres}, {Evanthia T.} and Ashani Weeraratna and Hariharan Easwaran and Fertig, {Elana J.}",

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AU - Erbe, Rossin

AU - Wang, Zheyu

AU - Wu, Sharon

AU - Xiu, Joanne

AU - Zaidi, Neeha

AU - La, Jennifer

AU - Tuck, David

AU - Fillmore, Nathanael

AU - Giraldo, Nicolas A.

AU - Topper, Michael

AU - Baylin, Stephen

AU - Lippman, Marc

AU - Isaacs, Claudine

AU - Basho, Reva

AU - Serebriiskii, Ilya

AU - Lenz, Heinz Josef

AU - Astsaturov, Igor

AU - Marshall, John

AU - Taverna, Josephine

AU - Lee, Jerry

AU - Jaffee, Elizabeth M.

AU - Roussos Torres, Evanthia T.

AU - Weeraratna, Ashani

AU - Easwaran, Hariharan

AU - Fertig, Elana J.

PY - 2021/8/24

Y1 - 2021/8/24

N2 - Both tumors and aging alter the immune landscape of tissues. These interactions may play an important role in tumor progression among elderly patients and may suggest considerations for patient care. We leverage large-scale genomic and clinical databases to perform comprehensive comparative analysis of molecular and cellular markers of immune checkpoint blockade (ICB) response with patient age. These analyses demonstrate that aging is associated with increased tumor mutational burden, increased expression and decreased promoter methylation of immune checkpoint genes, and increased interferon gamma signaling in older patients in many cancer types studied, all of which are expected to promote ICB efficacy. Concurrently, we observe age-related alterations that might be expected to reduce ICB efficacy, such as decreases in T cell receptor diversity. Altogether, these changes suggest the capacity for robust ICB response in many older patients, which may warrant large-scale prospective study on ICB therapies among patients of advanced age.

AB - Both tumors and aging alter the immune landscape of tissues. These interactions may play an important role in tumor progression among elderly patients and may suggest considerations for patient care. We leverage large-scale genomic and clinical databases to perform comprehensive comparative analysis of molecular and cellular markers of immune checkpoint blockade (ICB) response with patient age. These analyses demonstrate that aging is associated with increased tumor mutational burden, increased expression and decreased promoter methylation of immune checkpoint genes, and increased interferon gamma signaling in older patients in many cancer types studied, all of which are expected to promote ICB efficacy. Concurrently, we observe age-related alterations that might be expected to reduce ICB efficacy, such as decreases in T cell receptor diversity. Altogether, these changes suggest the capacity for robust ICB response in many older patients, which may warrant large-scale prospective study on ICB therapies among patients of advanced age.

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KW - immunotherapy

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Evaluating the impact of age on immune checkpoint therapy biomarkers

Abstract

Keywords

ASJC Scopus subject areas

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