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Establishment of a Co-culture System of Patient-Derived Colorectal Tumor Organoids and Tumor-Infiltrating Lymphocytes (TILs)
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Immunotherapy in Colorectal Cancer: Novel Perspectives and Next Steps
Thaís Sampaio Corrêa de Almeida1, Maria Ignez de Melro Freitas Braghiroli1,2, Jorge Sabbaga1,2
1IDOR Instituto D'Or de Pesquisa e Ensino - São Paulo, Brazil.
American Journal of Clinical Oncology
|August 14, 2026
Summary
Novel immunotherapies, including botensilimab and balstilimab, show promise for microsatellite-stable colorectal cancer (MSS CRC). This approach may extend immunotherapy benefits beyond MSI-H tumors, offering new treatment avenues for MSS CRC patients.
Area of Science:
- Oncology
- Immunotherapy
- Gastrointestinal Cancers
Background:
- Colorectal cancer (CRC) is a leading cause of cancer mortality globally.
- Microsatellite instability-high (MSI-H) CRC benefits from immune checkpoint inhibitors, but microsatellite-stable (MSS) CRC shows limited response.
- Novel immunotherapies are being investigated to improve outcomes for MSS CRC patients.
Purpose of the Study:
- To review recent advances and emerging perspectives on novel checkpoint inhibitors for MSS CRC.
- To analyze response outcomes in MSS CRC populations treated with botensilimab (BOT) and balstilimab (BAL).
- To assess the potential of immunotherapy beyond MSI-H CRC.
Main Methods:
- Structured review and critical analysis of relevant evidence on immunotherapy in CRC.
- Focus on response outcomes in MSS CRC treated with BOT+BAL combination therapy.
- Evaluation of efficacy in both refractory and neoadjuvant settings.
Main Results:
- BOT+BAL demonstrated objective response rates up to 20% and disease control rates around 60% in heavily pretreated/refractory MSS CRC.
- In the neoadjuvant setting, BOT+BAL achieved pathologic complete response (pCR) rates up to 40% and partial responses up to 71% in MSS CRC.
- Treatment was well-tolerated, with no surgical delays, and showed downstaging potential.
Conclusions:
- The combination of BOT+BAL shows significant promise for MSS CRC, potentially shifting the therapeutic landscape.
- Immunotherapy may offer new treatment possibilities for the broader MSS CRC patient population.
- Neoadjuvant BOT+BAL could spare surgery and/or adjuvant chemotherapy in MSS CRC.
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