Dataset Information

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.

SUBMITTER: Erbe R

PROVIDER: S-EPMC8757482 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Evaluating the impact of age on immune checkpoint therapy biomarkers.

Erbe Rossin R Wang Zheyu Z Wu Sharon S Xiu Joanne J Zaidi Neeha N La Jennifer J Tuck David D Fillmore Nathanael N Giraldo Nicolas A NA Topper Michael M Baylin Stephen S Lippman Marc M Isaacs Claudine C Basho Reva R Serebriiskii Ilya I Lenz Heinz-Josef HJ Astsaturov Igor I Marshall John J Taverna Josephine J Lee Jerry J Jaffee Elizabeth M EM Roussos Torres Evanthia T ET Weeraratna Ashani A Easwaran Hariharan H Fertig Elana J EJ

Cell reports 20210801 8

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 ...[more]

PMID: 34433020

Similar Datasets

Project description:BackgroundMore and more immune-oncology trials have been conducted for treating various cancers, yet it is unclear what the reporting quality of immune-oncology trials is,and characteristics associated with higher reporting quality.ObjectiveThis study aims to evaluate the reporting quality of immune-oncology trials.MethodsThe PubMed and Cochrane library were searched to identify all English publications of clinical trials assessing immunotherapy for cancer. Reporting quality of immune-oncology trials was evaluated by a quality score with 11 points derived from the Trial Reporting in Immuno-Oncology (TRIO) statement, which contained two parts: an efficacy score of 6 points and toxicity score of 5 point. Linear regression was used to identify characteristics associated with higher scores.ResultsOf the 10,169 studies screened, 298 immune-oncology trial reports were enrolled. The mean quality score, efficacy score, and toxicity score were 6.46, 3.61, and 2.85, respectively. The most common well-reported items were response evaluation criteria (96.0%) and toxicity grade (98.7%), followed by Kaplan-Meier survival analyses (80.5%). Treatment details beyond progression (12.8%) and toxicity onset time and duration (7.7%) were poorly reported. Multivariate regression revealed that higher impact factor (IF) (IF >20 vs. IF <5, p < 0.001), specific tumor type (p = 0.018 for lung, p = 0.021 for urinary system, vs. pan cancer), and a certain kind of immune checkpoint blocking agent (p < 0.001 for anti-PD-1 or multiagents, vs. anti-CTLA-4) were independent predictors of higher-quality score. Similar independent predictive characteristics were revealed for high-efficacy score. Only IF >20 had a significant high-toxicity score (p < 0.001).ConclusionImmune-oncology trial reports presented an unsatisfied quality score, especially in the reporting of treatment details beyond progression and toxicity onset time and duration. High IF journals have better reporting quality. Future improvement of trial reporting was warranted to the benefit-risk assessment of immunotherapy.

Dataset Information

Evaluating the impact of age on immune checkpoint therapy biomarkers.

Publications

Evaluating the impact of age on immune checkpoint therapy biomarkers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets