Immunotherapy in colorectal cancer: rationale, challenges and potential

Rákkutatás · Colorectal cancer · BRAF

Immunotherapy can provide durable remission in metastatic mismatch‑repair‑deficient colorectal cancer and is being explored in other subtypes.

Following initial successes in melanoma treatment, immunotherapy has rapidly become established as a major treatment modality for multiple types of solid cancers, including a subset of colorectal cancers (CRCs). Two programmed cell death 1 (PD1)-blocking antibodies, pembrolizumab and nivolumab, have shown efficacy in patients with metastatic CRC that is mismatch‑repair‑deficient and microsatellite instability‑high (dMMR–MSI‑H), and have been granted accelerated FDA approval. In contrast to most other treatments for metastatic cancer, immunotherapy achieves long‑term durable remission in a subset of patients, highlighting the tremendous promise of immunotherapy in treating dMMR–MSI‑H metastatic CRC. Here, we review the clinical development of immune checkpoint inhibition in CRC leading to regulatory approvals for the treatment of dMMR–MSI‑H CRC. We focus on new advances in expanding the efficacy of immunotherapy to early‑stage CRC and CRC that is mismatch‑repair‑proficient and has low microsatellite instability (pMMR–MSI‑L) and discuss emerging approaches for targeting the immune microenvironment, which might complement immune checkpoint inhibition.

Colorectal cancer remains one of the leading causes of cancer‑related mortality worldwide. Traditional chemotherapeutic regimens offer limited long‑term survival for metastatic disease. The emergence of immune checkpoint inhibitors—particularly anti‑PD‑1 antibodies such as pembrolizumab and nivolumab—has altered this paradigm for a specific biomarker‑defined subset: mismatch‑repair‑deficient or microsatellite instability‑high (dMMR‑MSI‑H) CRC. These agents have demonstrated durable responses and improved overall survival, leading to accelerated FDA approval. Continued research into expanding efficacy to mismatch‑repair‑proficient tumors, combination therapies, and early‑stage disease holds promise for broadening the therapeutic benefit to a larger CRC patient population.

Bizonyítékszint: Állatkísérletes. Állatmodellben vizsgálták.

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