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Published on: February 25, 2020
Predictors of sensitivity to immune therapies in classic Hodgkin lymphoma
Mohamed Nazem Alibrahim1, Antonino Carbone2, Annunziata Gloghini3
1Department of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Abstract:
Immune checkpoint blockade, particularly programmed cell death protein 1 inhibition, has redefined the management of classic Hodgkin lymphoma (cHL), achieving unprecedented efficacy in relapsed/refractory settings. Yet, durable benefit is not universal, because mechanisms of primary and acquired resistance remain incompletely understood. This review integrates current knowledge on predictors of sensitivity to immune therapies in cHL across clinical, biological, and technological dimensions. Established predictors, including disease burden, previous treatment exposure, CD30 intensity, programmed death-ligand 1 (PD-L1)/PD-L2 copy number gains, and loss of major histocompatibility complex expression, offer valuable but incomplete prognostic information. Tumor microenvironmental features such as macrophage polarization, T-cell exhaustion, and immune spatial organization further refine response prediction, whereas circulating biomarkers such as soluble PD-L1, circulating tumor DNA kinetics, and cytokine profiles provide noninvasive insights. Molecular and cellular pathways underlying resistance encompass genetic and epigenetic alterations, immune editing, and adaptive checkpoint upregulation. Emerging predictive frameworks, spanning multiomics and spatial profiling, radiomics, artificial intelligence, and microbiome-host cross talk, promise to enhance precision in patient stratification. Finally, the review outlines key challenges and research priorities for translating these multidimensional biomarkers into clinical trials and practice. A unified predictive framework integrating clinical, molecular, and computational indicators may ultimately enable personalized immunotherapy and overcome resistance in cHL.
Insights
Predicting response to immune checkpoint blockade in classic Hodgkin lymphoma (cHL) is crucial. This review integrates clinical, biological, and technological predictors to improve patient stratification and overcome resistance to immunotherapy.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Immune checkpoint blockade, especially programmed cell death protein 1 (PD-1) inhibition, has transformed classic Hodgkin lymphoma (cHL) treatment for relapsed/refractory cases.
- However, not all patients achieve durable responses, and the mechanisms of primary and acquired resistance are not fully understood.
Purpose of the Study:
- To review and integrate current knowledge on predictors of sensitivity to immune therapies in cHL.
- To explore established and emerging biomarkers across clinical, biological, and technological dimensions for improved patient stratification.
Main Methods:
- Review of existing literature on predictors of immune therapy response in cHL.
- Integration of clinical factors (disease burden, prior treatment), biological markers (CD30 intensity, PD-L1/PD-L2 copy number gains, MHC expression), and tumor microenvironment features (macrophage polarization, T-cell exhaustion, immune spatial organization).
- Inclusion of circulating biomarkers (soluble PD-L1, ctDNA kinetics, cytokine profiles) and emerging predictive frameworks (multiomics, spatial profiling, radiomics, AI, microbiome).
Main Results:
- Established predictors provide valuable but incomplete prognostic information.
- Tumor microenvironment and circulating biomarkers offer refined and noninvasive insights into response prediction.
- Resistance mechanisms involve genetic/epigenetic alterations, immune editing, and adaptive checkpoint upregulation.
Conclusions:
- A multidimensional approach integrating clinical, molecular, and computational indicators is needed for precise patient stratification.
- Emerging predictive frameworks hold promise for enhancing personalized immunotherapy strategies in cHL.
- Further research is required to translate these biomarkers into clinical practice and overcome immunotherapy resistance.
