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Published on: February 25, 2020
Immune checkpoint inhibitors in sarcomas: in quest of predictive biomarkers
Robin Veenstra1, Marie Kostine1, Anne-Marie Cleton-Jansen1
1Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Abstract:
Sarcomas are a rare group of tumors of mesenchymal origin. Metastatic sarcomas are often difficult to treat and unresponsive to standard radio- and chemotherapy, resulting in a poor survival rate for patients. Novel treatments with immune checkpoint inhibitors have been proven to prolong survival of patients with a variety of cancers, including metastatic melanoma, lung, and renal cell carcinoma. Since immune checkpoint inhibitors could provide a novel treatment option for patients with sarcomas, clinical trials investigating their efficacy in these group of tumors are ongoing. However, the discrimination of patients that are the most likely to respond to these treatments is still an obstacle in the design of clinical trials. In this review, we provide a brief overview of the mechanisms of action of immune checkpoint inhibitors and discuss the proposed biomarkers of therapy response, such as lymphocytic infiltration, intratumoral PD-L1 expression, and mutational load in sarcomas.
Insights
Immune checkpoint inhibitors show promise for treating metastatic sarcomas. Identifying biomarkers like lymphocytic infiltration and PD-L1 expression is crucial for patient selection in clinical trials.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Sarcomas are rare mesenchymal tumors with poor prognosis in metastatic stages.
- Standard treatments are often ineffective, necessitating novel therapeutic approaches.
- Immune checkpoint inhibitors (ICIs) have shown success in other metastatic cancers.
Purpose of the Study:
- To review the mechanism of action of ICIs.
- To discuss potential biomarkers for predicting ICI response in sarcoma patients.
- To highlight challenges in patient stratification for clinical trials.
Main Methods:
- Review of existing literature on immune checkpoint inhibitors and sarcoma.
- Analysis of proposed biomarkers including lymphocytic infiltration, PD-L1 expression, and tumor mutational burden.
- Discussion of clinical trial design considerations.
Main Results:
- ICIs represent a potential new treatment avenue for metastatic sarcomas.
- Biomarkers such as lymphocytic infiltration, intratumoral PD-L1 expression, and mutational load are being investigated.
- Patient selection remains a key challenge for optimizing ICI therapy in sarcomas.
Conclusions:
- Immune checkpoint inhibitors offer a novel therapeutic strategy for metastatic sarcomas.
- Identifying predictive biomarkers is essential for effective patient stratification and treatment.
- Further research is needed to elucidate the role of ICIs and associated biomarkers in sarcoma management.
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