Immunotherapy Strategies in Colorectal Cancer Treatment

Immunotherapy harnesses the patient’s immune system to recognise and eliminate colorectal tumours through a range of approaches, including immune checkpoint blockade, adoptive cell transfer, cancer vaccines and combination regimens. Tumours with deficient mismatch repair and high microsatellite instability generate abundant neoantigens, rendering them particularly responsive to PD-1/PD-L1 inhibitors, whereas microsatellite-stable cancers often require multi-modal strategies to overcome a suppressive microenvironment. Small-molecule inhibitors targeting angiogenesis and tyrosine kinases have been shown to remodel the tumour milieu, facilitating T cell infiltration. Concurrent modulation of the gut microbiome and biomarker-driven patient selection are emerging as pivotal factors in optimising clinical benefit. Current research is devoted to expanding efficacy beyond the small subset of hypermutated tumours by integrating radiotherapy, targeted agents and novel immunomodulators, with the ultimate goal of improving response rates and prolonging survival in advanced colorectal cancer.

Research from Nature Portfolio

Phase II findings from a study of cabozantinib plus durvalumab in chemorefractory colorectal cancer patients with proficient mismatch repair and microsatellite stability revealed an objective response rate of 27.6% and manageable toxicity. Exploratory spatial transcriptomic profiling demonstrated that responders exhibited upregulated VEGF and MET signalling, increased extracellular matrix remodelling and coexisting pro-inflammatory immune infiltrates alongside T cell migration barriers. These data support a strategy of dual targeting of angiogenic pathways and immune checkpoints to overcome intrinsic resistance mechanisms.

Immunotherapy Strategies in Colorectal Cancer Treatment publication trend

The graph below shows the total number of articles in immunotherapy strategies in colorectal cancer treatment across all publications each year (not limited to Nature Index journals).

Technical terms

Microsatellite instability (MSI): Genetic hypermutability arising from defective DNA mismatch repair, associated with high neoantigen load and enhanced sensitivity to checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs): Antibodies that block regulatory molecules such as PD-1, PD-L1 or CTLA-4, thereby reinvigorating T cell-mediated antitumour responses.

Spatial transcriptomics: A technique mapping gene expression within the spatial context of tissue, enabling analysis of cellular interactions in the tumour microenvironment.

Tumour mutation burden (TMB): The total count of somatic mutations per coding megabase of the tumour genome, used as a biomarker to predict immunotherapy response.

References

1. Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy. Signal Transduction and Targeted Therapy (2024).
2. An international phase II trial and immune profiling of SBRT and atezolizumab in advanced pretreated colorectal cancer. Molecular Cancer (2024).
3. Clinical and biomarker results from a phase II trial of combined cabozantinib and durvalumab in patients with chemotherapy-refractory colorectal cancer (CRC): CAMILLA CRC cohort. Nature Communications (2024).
4. Regorafenib plus toripalimab in patients with metastatic colorectal cancer: a phase Ib/II clinical trial and gut microbiome analysis. Cell Reports Medicine (2021).
5. Colorectal Cancer Immunotherapy: Options and Strategies. Frontiers in Immunology (2020).