Immunotherapy for colorectal cancer: where are we heading?

ABSTRACT

Introduction: In the last few years, significant advances in molecular biology have provided new therapeutic options for colorectal cancer (CRC). The development of new drugs that target the immune response to cancer cells seems very promising and has already been established for other tumor types. In particular, the use of immune checkpoint inhibitors seems to be an encouraging immunotherapeutic strategy.

Areas covered: In this review, the authors provide an update of the current evidence related to this topic, though most immunotherapies are still in early-phase clinical trials for CRC. To understand the key role of immunotherapy in CRC, the authors discuss the delicate balance between immune-stimulating and immune-suppressive networks that occur in the tumor microenvironment.

Expert opinion: Modulation of the immune system through checkpoint inhibition is an emerging approach in CRC therapy. Nevertheless, selection criteria that could enable the identification of patients who may benefit from these agents are necessary. Furthermore, potential prognostic and predictive immune biomarkers based on immune and molecular classifications have been proposed. As expected, additional studies are required to develop biomarkers, effective therapeutic strategies and novel combinations to overcome immune escape resistance and enhance effector response.

KEYWORDS:

• Immunotherapy
• colorectal cancer
• PD-L1
• MSI
• pembrolizumab
• atezolizumab

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Erratum

Article highlights

• Immunotherapy is a promising therapeutic option in the treatment of many types of cancer. Currently, many clinical trials are evaluating the safety, activity, and efficacy of these agents in patients with colorectal cancer (CRC).

• Increased knowledge of the tumor microenvironment is key to developing innovative strategies and novel drugs.

• It is essential to identify new potential predictive and prognostic immune biomarkers that could have a clinical impact on patient selection and may guide treatment options. In this landscape, tumor infiltrating lymphocytes (TILs) within human CRC tumors have a critical impact on patient outcome.

• CMS1, which includes tumors with microsatellite instability (MSI), is the most immunogenic CRC subgroup. Therefore, patients with CMS1 and TIL-positive tumors could benefit from checkpoint inhibitors.

• Cancer cells may escape immune surveillance and develop resistance to immunotherapy by acquiring genetic alterations. Consequently, some patients exhibit primary or acquired resistance.

• There is a complex relationship between immunity, inflammation, and cancer. Preclinical studies have demonstrated the potential benefit of combining checkpoint inhibitors and anti-COX-2 therapy.

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Acknowledgments

We would like to thank Masoud Saman of Otolaryngology and Facial Plastic Surgery, Fort Worth, Texas, U.S.A., for his help with language editing. The authors also acknowledge language editing from Taylor & Francis Editing Services.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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Funding

This manuscript has not been funded.