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Published on: April 22, 2019
Immunological Checkpoint Blockade in Anal Squamous Cell Carcinoma: Dramatic Responses Tempered By Frequent Resistance
Thejus Jayakrishnan1, Devvrat Yadav2, Brandon M Huffman3,4
1Department of Hematology-Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, USA.
Purpose Of Review:
Squamous cell carcinoma of the anus (SCCA) is an HPV-associated malignancy that has limited treatment options. Immunotherapy has expanded these options and here we review current and emerging immunotherapeutic approaches.
Recent Findings:
Multiple studies of single-agent anti-PD1/PD-L1 immunotherapy have demonstrated a modest response rate of approximately 10% to 15%. While a minority of patients (~5%) with SCCA experience durable complete responses, most advanced SCCAs are resistant to anti-PD1/PD-L1 monotherapy. Given the need for more broadly effective immunotherapies, novel strategies, such as adaptive cell therapies and therapeutic vaccination, are being explored. To reduce the recurrence risk of localized high-risk SCCA, strategies combining immunotherapy with chemoradiation are also being investigated. While a small subset of patients with SCCA have prolonged responses to PD1-directed immunotherapy, the majority do not derive clinical benefit, and new immunotherapeutic strategies are needed. Better understanding of the immune microenvironment and predictive biomarkers could accelerate therapeutic advances.
Insights
Immunotherapy offers new options for anal squamous cell carcinoma (SCCA), but current anti-PD1/PD-L1 treatments show limited success. Novel strategies like cell therapies and vaccination are under investigation for improved SCCA treatment.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Squamous cell carcinoma of the anus (SCCA) is an HPV-associated cancer with limited therapeutic choices.
- Immunotherapy has emerged as a promising avenue for treating SCCA.
Purpose of the Study:
- To review current and emerging immunotherapeutic strategies for SCCA.
- To assess the efficacy and limitations of existing immunotherapies for SCCA.
Main Methods:
- Review of clinical studies on anti-PD1/PD-L1 immunotherapies for SCCA.
- Exploration of novel approaches including adaptive cell therapies and therapeutic vaccination.
- Investigation of combination strategies with chemoradiation for localized SCCA.
Main Results:
- Single-agent anti-PD1/PD-L1 immunotherapy yields modest response rates (10-15%) in SCCA.
- Durable complete responses are rare (~5%), with most advanced SCCAs showing resistance to monotherapy.
- New strategies are needed as the majority of patients do not benefit from current PD1-directed therapies.
Conclusions:
- While immunotherapy has expanded SCCA treatment options, current approaches have limitations.
- Novel immunotherapeutic strategies, including cell therapies and vaccination, are under active investigation.
- Further research into the tumor immune microenvironment and predictive biomarkers is crucial for advancing SCCA treatment.
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