Related Experiment Video
Updated: Mar 12, 2026
Assessment of Human Natural Killer Cell Events Driven by FcγRIIIa Engagement in the Presence of Therapeutic Antibodies
Published on: May 22, 2020
Characterizing CD137 upregulation on NK cells in patients receiving monoclonal antibody therapy
A Makkouk1, V Sundaram2, C Chester1,3
1Department of Medicine, Division of Oncology, Stanford University , Stanford, CA, USA.
Background:
In the era of personalized cancer medicine, identifying techniques for effectively matching patients to efficacious treatments is a critical step in the treatment process. The advent of anti-cancer immunotherapies necessitates novel approaches to biomarker identification beyond traditional genomic profiling. One promising approach is incorporation of nomograms into treatment decisions. Nomograms are prediction tools, based on statistical modeling, designed to predict treatment outcomes. As a first step toward developing a nomogram, we conducted analyses to predict CD137 expression of natural killer cells after monoclonal antibody (mAb) treatment.
Patients And Methods:
Patient, tumor and immune characteristics were collected from 199 patients with breast cancer (N = 62), head/neck cancers (N = 46) and non-Hodgkin's lymphoma (NHL) (N = 91), who were receiving mAb therapy as part of clinical trials. The difference in CD137 expression before and after mAb therapy was assessed by flow cytometry. To evaluate those who respond to mAb therapy via increased CD137 expression, we applied classification and regression trees (CART), multivariable lasso regression tools and Random Forest.
Results:
The CD137 expression was significantly different for each cancer type [mean (SD): Breast: 6.6 (6.5); Head/Neck: 11.0 (7.0); NHL: 7.5 (7.1), P < 0.0001]. For breast cancer and NHL, FcR polymorphism and baseline CD137 expression were significant predictors of increased CD137 expression; for head/neck cancer, FcR polymorphism and age were significant predictors of increased expression.
Conclusions:
Our preliminary results suggest that FcR polymorphism, pre-treatment CD137 expression and age are significant predictors of CD137 upregulation in patients. This study demonstrates that the development of a nomogram for therapy response is feasible. Further work validating our models in an independent cohort will provide the next steps in developing a nomogram that may be used to individualize this therapeutic approach for patients (NCT01114256).
Insights
Predicting cancer treatment response is key for personalized medicine. FcR polymorphism, baseline CD137 expression, and age predict natural killer cell CD137 upregulation after monoclonal antibody therapy.
Area of Science:
- Oncology
- Immunology
- Biostatistics
Background:
- Personalized cancer medicine requires effective patient-treatment matching.
- Anti-cancer immunotherapies demand novel biomarkers beyond genomics.
- Nomograms offer a promising approach for predicting treatment outcomes.
Purpose of the Study:
- To analyze predictors of CD137 expression on natural killer cells post-monoclonal antibody (mAb) treatment.
- To establish a foundation for developing a nomogram to guide personalized cancer therapy.
Main Methods:
- Collected data from 199 patients with breast, head/neck cancers, and non-Hodgkin's lymphoma receiving mAb therapy.
- Assessed CD137 expression changes using flow cytometry.
- Applied classification and regression trees, lasso regression, and Random Forest models.
Main Results:
- CD137 expression varied significantly across cancer types (P < 0.0001).
- FcR polymorphism and baseline CD137 predicted upregulation in breast and NHL.
- FcR polymorphism and age predicted upregulation in head/neck cancer.
Conclusions:
- FcR polymorphism, baseline CD137, and age are significant predictors of CD137 upregulation.
- Developing a nomogram for therapy response prediction is feasible.
- Further validation in independent cohorts is needed to individualize treatment.
Related Concept Videos
01:27Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
01:22T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...