Evaluating the impact of age on immune checkpoint therapy biomarkers

Rossin Erbe; Z. Wang; S Wu; Joanne Xiu; Neeha Zaidi; J La; D Tuck; Nathanael Fillmore; Nicolas A. Giraldo; Michael Topper; S Baylin; Marc Lippman; Claudine Isaacs; Reva Basho; I Serebriiskii; HJ Lenz; Igor Astsaturov; J Marshall; J Taverna; J. Lee; Elizabeth M. Jaffee; Evanthia T. Roussos Torres; Ashani T. 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, Z. Wang, S Wu, Joanne Xiu, Neeha Zaidi, J La, D Tuck, Nathanael Fillmore, Nicolas A. Giraldo, Michael Topper, S Baylin, Marc Lippman, Claudine Isaacs, Reva Basho, I Serebriiskii, HJ Lenz, Igor Astsaturov, J Marshall, J Taverna, J. LeeElizabeth M. Jaffee, Evanthia T. Roussos Torres, Ashani T. Weeraratna, Hariharan Easwaran, Elana J. Fertig

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32 Scopus citations

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
Article number	109599
Pages (from-to)	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

Age Factors
B7-H1 Antigen/genetics
Biomarkers, Tumor/genetics
Genomics
Humans
Immunotherapy/methods
Neoplasms/drug therapy
Prospective Studies

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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, HJ., Astsaturov, I., Marshall, J., Taverna, J., ... Fertig, E. J. (2021). Evaluating the impact of age on immune checkpoint therapy biomarkers. Cell Reports, 36(8), 109599. Article 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.",

keywords = "Age Factors, B7-H1 Antigen/genetics, Biomarkers, Tumor/genetics, Genomics, Humans, Immunotherapy/methods, Neoplasms/drug therapy, Prospective Studies",

author = "Rossin Erbe and Z. Wang and S Wu and Joanne Xiu and Neeha Zaidi and J La and D Tuck and Nathanael Fillmore and Giraldo, {Nicolas A.} and Michael Topper and S Baylin and Marc Lippman and Claudine Isaacs and Reva Basho and I Serebriiskii and HJ Lenz and Igor Astsaturov and J Marshall and J Taverna and J. Lee and Jaffee, {Elizabeth M.} and {Roussos Torres}, {Evanthia T.} and Weeraratna, {Ashani T.} and Hariharan Easwaran and Fertig, {Elana J.}",

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s)",

year = "2021",

month = aug,

day = "24",

doi = "10.1016/j.celrep.2021.109599",

language = "English",

volume = "36",

pages = "109599",

journal = "Cell Reports",

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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, AT, Easwaran, H & Fertig, EJ 2021, 'Evaluating the impact of age on immune checkpoint therapy biomarkers', Cell Reports, vol. 36, no. 8, 109599, pp. 109599. https://doi.org/10.1016/j.celrep.2021.109599

TY - JOUR

T1 - Evaluating the impact of age on immune checkpoint therapy biomarkers

AU - Erbe, Rossin

AU - Wang, Z.

AU - Wu, S

AU - Xiu, Joanne

AU - Zaidi, Neeha

AU - La, J

AU - Tuck, D

AU - Fillmore, Nathanael

AU - Giraldo, Nicolas A.

AU - Topper, Michael

AU - Baylin, S

AU - Lippman, Marc

AU - Isaacs, Claudine

AU - Basho, Reva

AU - Serebriiskii, I

AU - Lenz, HJ

AU - Astsaturov, Igor

AU - Marshall, J

AU - Taverna, J

AU - Lee, J.

AU - Jaffee, Elizabeth M.

AU - Roussos Torres, Evanthia T.

AU - Weeraratna, Ashani T.

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.

KW - Age Factors

KW - B7-H1 Antigen/genetics

KW - Biomarkers, Tumor/genetics

KW - Genomics

KW - Humans

KW - Immunotherapy/methods

KW - Neoplasms/drug therapy

KW - Prospective Studies

UR - http://www.scopus.com/inward/record.url?scp=85113394240&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2021.109599

DO - 10.1016/j.celrep.2021.109599

M3 - Article

C2 - 34433020

SN - 2211-1247

VL - 36

SP - 109599

JO - Cell Reports

JF - Cell Reports

IS - 8

M1 - 109599

ER -

Evaluating the impact of age on immune checkpoint therapy biomarkers

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Keywords

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