Immunotherapy for Microsatellite-Stable Metastatic Colorectal Cancer - Can we close the Gap between Potential and Practice?

Sep 21, 2026

Uploaded by Rowan

Review article examining strategies to make microsatellite-stable metastatic colorectal cancer (MSS mCRC) susceptible to immune checkpoint inhibitors (ICI). It summarizes why CRC remains a leading cause of cancer death despite improved early-stage outcomes, and explains that most metastatic patients are MSS where ICIs have limited efficacy. The review highlights the need to address primary resistance in MSS disease and discusses candidate biomarkers for better patient selection and ongoing research directions.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Abstract

Purpose of Review

Recent Findings

Summary

Introduction

Current Oncology Reports (2024) 26:1258–1270 [https://doi.org/10.1007/s1](https://doi.org/10.1007/s1) 1912-024-01583-w Immunotherapy for Microsatellite‑Stable Metastatic Colorectal Cancer: Can we close the Gap between Potential and Practice? Marwa Abdel Hamid1 · Lorenz M. Pammer2 · Theresa K. Lentner3 · Bernhard Doleschal4,5 · Rebecca Gruber1 · Florian Kocher1 · Elisabeth Gasser6 · Anna Jöbstl7 · Andreas Seeber1 · Arno Amann1 Accepted: 11 July 2024 / Published online: 30 July 2024 © The Author(s) 2024 Abstract Purpose of Review This review will explore various strategies to rendering MSS mCRCs susceptible to ICI. Moreover, we will provide an overview of potential biomarkers that may aid to better patient selection, and discuss ongoing efforts in this area of research. Recent Findings Colorectal cancer (CRC) ranks among the top three most common cancers worldwide. While significant advances in treatment strategies have improved the prognosis for patients in the early stages of the disease, treatment options for metastatic CRC (mCRC) remain limited. Although immune checkpoint inhibitors (ICI) have revolutionized the treatment of several malignancies, its efficacy in mCRC is largely confined to patients exhibiting a high microsatellite instability status (MSI-H). However, the vast majority of mCRC patients do not exhibit a MSI-H, but are microsatellite stable (MSS) . In these patients ICIs are largely ineffective. Summary So far, ICIs do not play a crucial role in patients with MSS mCRC, despite the promising data for inducing longterm remissions in other tumour entities. For this reason, novel treatment strategies are needed to overcome the primary resistance upon ICI in patients with MSS. Keywords Colorectal cancer · Immunotherapy · Biomarker · Microsatellite stable · Microsatellite instability Marwa Abdel Hamid, Lorenz M. Pammer, Andreas Seeber, Arno Amann are contributed equally to this work. * Arno Amann [arno.amann@tirol-kliniken.at](arno.amann@tirol-kliniken.at) 1 Department of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria 2 Department of Gastroenterology and Hepatology, Medical University of Innsbruck, Innsbruck, Austria 3 Clinical Department for Internal Medicine, University Hospital St. Poelten, Karl Landsteiner University of Health Sciences, St. Poelten, Austria 4 Department of Internal Medicine I for Hematology With Stem Cell Transplantation, Hemostaseology and Medical Oncology, Ordensklinikum Linz, Linz, Austria 5 Medical Faculty, Johannes Kepler University Linz, Linz, Austria 6 Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria 7 Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria Introduction Colorectal cancer (CRC) is the third most common cancer globally, and represents the second most common malignant tumor in women and the third most common in men [1] . The prognosis of patients with CRC depends on the stage of disease at initial diagnosis and other clinical and biological risk factors [2]. Regrettably, around 50% of patients are diagnosed at an advanced stage initially [3]. Although great advances in the treatment of advanced or metastasized CRC (mCRC) have been achieved, it remains one of the leading causes of death worldwide [2] . In recent decades, a significant wave of approved targeted therapeutics has been integrated into clinical practice. Understanding molecular signaling networks that control intestinal regeneration and homeostasis has helped to discover key drivers in CRC pathogenesis, progression and novel treatment targets [4] . Molecular profiling and tumor characterization, including chromosomal instability, microsatellite instability (MSI), and the CpG island methylator phenotype, have thus, become essential tools in guiding clinical decision making [3].

FAQs

Why are immune checkpoint inhibitors mostly ineffective for microsatellite-stable metastatic colorectal cancer (MSS mCRC)?

The review explains that ICIs show largely limited efficacy in MSS mCRC, while effectiveness is mostly confined to patients with high microsatellite instability (MSI-H). As most mCRC patients are MSS, the outcomes with ICIs are generally poor.

What research goal does the review focus on for MSS mCRC?

The review aims to explore strategies that could render MSS mCRCs susceptible to ICI, thereby moving beyond the current gap between potential responses and real-world practice.

How do biomarkers fit into improving patient selection for ICI therapy?

The review discusses potential biomarkers that may help identify which patients are more likely to benefit from ICI treatment, supporting better patient selection in ongoing research.

Sep 21, 2026

Uploaded by Rowan