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Age-Related Differences in Molecular Profiles for Immune Checkpoint Blockade Therapy
Qi-Jie Zhang1, Jiao-Chen Luan1, Le-Bin Song2
1Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Abstract:
Immune checkpoint blockade (ICB) therapies have significantly improved the prognosis and shown considerable promise for cancer therapy; however, differences in ICB treatment efficacy between the elderly and young are unknown. We analyzed the studies enrolled in the meta-analysis using the deft approach, and found no difference in efficacy except melanoma patients receiving anti-PD-1 therapy. Similarly, higher treatment response rate and more favorable prognosis were observed in elderly patients in some cancer types (e.g., melanoma) with data from published ICB treatment clinical trials. In addition, we comprehensively compared immunotherapy-related molecular profiles between elderly and young patients from public trials and The Cancer Genome Atlas (TCGA), and validated these findings in several independent datasets. We discovered a divergent age-biased immune profiling, including the properties of tumors (e.g., tumor mutation load) and immune features (e.g., immune cells), in a pancancer setting across 27 cancer types. We believe that ICB treatment efficacy might vary depending on specific cancer types and be determined by both the tumor internal features and external immune microenvironment. Considering the high mutational properties in elderly patients in many cancer types, modulating immune function could be beneficial to immunotherapy in the elderly, which requires further investigation.
Insights
Immune checkpoint blockade (ICB) therapy efficacy shows no significant age difference overall, but elderly melanoma patients receiving anti-PD-1 therapy benefit more. Age-biased immune profiles were observed across 27 cancer types.
Area of Science:
- Oncology
- Immunology
- Geriatrics
Background:
- Immune checkpoint blockade (ICB) therapies have revolutionized cancer treatment.
- The impact of patient age on ICB efficacy remains largely unknown.
- Understanding age-related differences is crucial for optimizing cancer immunotherapy.
Purpose of the Study:
- To investigate age-based differences in ICB treatment efficacy across various cancer types.
- To compare molecular profiles related to immunotherapy response between elderly and young patients.
- To identify age-biased immune characteristics influencing treatment outcomes.
Main Methods:
- Meta-analysis of published clinical trials using the deft approach.
- Comparison of immunotherapy-related molecular profiles from public trials and The Cancer Genome Atlas (TCGA).
- Validation of findings in independent datasets across 27 cancer types.
Main Results:
- No significant difference in ICB efficacy between elderly and young patients, except for melanoma patients receiving anti-PD-1 therapy.
- Elderly patients showed higher response rates and better prognosis in specific cancers like melanoma.
- Discovered divergent age-biased immune profiling, including tumor and immune cell features, in a pancancer setting.
Conclusions:
- ICB efficacy may vary by cancer type and be influenced by tumor-intrinsic and microenvironmental factors.
- Elderly patients exhibit distinct mutational properties in many cancer types, suggesting potential benefits from immune function modulation.
- Further research is needed to explore targeted immunotherapies for elderly cancer patients.
