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Aging-related biomarker discovery in the era of immune checkpoint inhibitors for cancer patients.

ABSTRACT: Older patients with cancer, particularly those over 75 years of age, often experience poorer clinical outcomes compared to younger patients. This can be attributed to age-related comorbidities, weakened immune function, and reduced tolerance to treatment-related adverse effects. In the immune checkpoint inhibitors (ICI) era, age has emerged as an influential factor impacting the discovery of predictive biomarkers for ICI treatment. These age-linked changes in the immune system can influence the composition and functionality of tumor-infiltrating immune cells (TIICs) that play a crucial role in the cancer response. Older patients may have lower levels of TIICs infiltration due to age-related immune senescence particularly T cell function, which can limit the effectivity of cancer immunotherapies. Furthermore, age-related immune dysregulation increases the exhaustion of immune cells, characterized by the dysregulation of ICI-related biomarkers and a dampened response to ICI. Our review aims to provide a comprehensive understanding of the mechanisms that contribute to the impact of age on ICI-related biomarkers and ICI response. Understanding these mechanisms will facilitate the development of treatment approaches tailored to elderly individuals with cancer.

SUBMITTER: Al-Danakh A

PROVIDER: S-EPMC11000233 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Aging-related biomarker discovery in the era of immune checkpoint inhibitors for cancer patients.

Al-Danakh Abdullah A Safi Mohammed M Jian Yuli Y Yang Linlin L Zhu Xinqing X Chen Qiwei Q Yang Kangkang K Wang Shujing S Zhang Jianjun J Yang Deyong D

Frontiers in immunology 20240315

Older patients with cancer, particularly those over 75 years of age, often experience poorer clinical outcomes compared to younger patients. This can be attributed to age-related comorbidities, weakened immune function, and reduced tolerance to treatment-related adverse effects. In the immune checkpoint inhibitors (ICI) era, age has emerged as an influential factor impacting the discovery of predictive biomarkers for ICI treatment. These age-linked changes in the immune system can influence the ...[more]

PMID: 38590525

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Project description:ImportanceAlthough immune checkpoint inhibitors (ICIs), such as anti-PD-1 (programmed cell death 1) or anti-PD-L1 (programmed cell death 1 ligand 1), have proved effective in treating many cancers, patients receiving ICIs may experience immune-related adverse events (irAEs). Little evidence exists on the safety of resuming these treatments after an irAE.ObjectiveTo investigate the safety of a rechallenge with anti-PD-1 or anti-PD-L1 immunotherapies after an irAE.Design, setting, and participantsThis cohort study of the safety of an ICI rechallenge involved consecutive adult patients (n = 93) who were referred to the ImmunoTOX assessment board at the Gustave Roussy cancer center in Villejuif, France, between August 1, 2015, and December 31, 2017. Data were analyzed from May 28 to November 25, 2018.Main outcomes and measuresIncidence of a second irAE in patients who had a readministration of an anti-PD-1 or anti-PD-L1 inhibitor after an initial grade 2 or higher irAE. Characteristics of the patients and the irAEs were reviewed, and the primary end point was the rate of occurrence of second irAEs.ResultsA total of 93 patients were included, among whom 48 (52%) were female, and the median (range) age was 62.5 (33-85) years. The main cancer types or tumor sites were melanoma (31 [33%]), lung (15 [16%]), colorectal (8 [9%]), and lymphoma (8 [9%]). For the initial irAE, 43 grade 2 events (46%), 36 grade 3 events (39%), and 14 grade 4 events (15%) were found, presenting primarily as hepatitis (17 [18%]), skin toxic effect (14 [15%]), pneumonitis (13 [14%]), colitis (11 [12%]), or arthralgia (7 [7.5%]). Forty patients (43%) were rechallenged with the same anti-PD-1 or anti-PD-L1 agent. The rechallenged and non-rechallenged groups did not differ in terms of median (range) age (61 [34-84] years vs 63 [33-85] years; P = .37), time to initial irAE (5 [1-40] treatment cycles vs 3 [1-22] treatment cycles; P = .32), irAE severity (grade 2: 18 [47.5%] vs 27 [51%]; grades 3-4: 22 [52.5%] vs 26 [49%]; P = .70), or steroid use (17 [42.5%] vs 32 [60%]; P = .09). With a median follow-up period of 14 months, the same irAE or a different irAE occurred in 22 patients (55%). Shorter time to the initial irAE was linked to the occurrence of a second irAE (9 vs 15 weeks; P = .04). The second irAEs were not found to be more severe than the first.Conclusions and relevanceThe risk-reward ratio for an anti-PD-1 or anti-PD-L1 rechallenge appears to be acceptable, although these patients require close monitoring; further investigation into rechallenge conditions through a prospective clinical trial is needed.

Dataset Information

Aging-related biomarker discovery in the era of immune checkpoint inhibitors for cancer patients.

Publications

Aging-related biomarker discovery in the era of immune checkpoint inhibitors for cancer patients.

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