Acquired Immunotherapy Resistance in Gastrointestinal Cancers

Finally, there remains a critical gap in our understanding of how to best treat patients with cancer that are considered refractory to ICI-based therapies.Using data from the Table in the article by Zhuo et al, 1 we calculate that the rates of AR were similar in patients who received ICI alone vs ICI in combination with other systemic therapies (68 of 152 patients [44.7%] vs 105 of 221 patients [47.5%]).Additionally, subsequent systemic and/or local therapies led to similar overall survival (median 26.1 months [95% CI, 12.5-40.0months]), indicating that a cookie-cutter approach to overcoming AR does not appear to be effective.Resistance to ICI, whether primary or acquired, appears to stem from a variety of proposed mechanisms, ranging from defective antigen presentation to upregulated immunosuppression.7 Taken together, individualizing therapeutic strategies according to biomarker-driven research will likely hold the key to success.In conclusion, although current understanding of resistance mechanisms to ICI is incomplete, the critical foundation for future directions in clearing the confusion is being laid out.