Genetic immune escape in cancer: timing and implications for treatment

Abstract

Immunotherapy resistance; Tumor evolution; Tumor microenvironment

Resistencia a la inmunoterapia; Evolución del tumor; Microambiente tumoral

Resistència a la immunoteràpia; Evolució del tumor; Microambient tumoral

Genetic immune escape (GIE) alterations pose a significant challenge in cancer by enabling tumors to evade immune detection. These alterations, which can vary significantly across cancer types, may often arise early in clonal evolution and contribute to malignant transformation. As tumors evolve, GIE alterations are positively selected, allowing immune-resistant clones to proliferate. In addition to genetic changes, the tumor microenvironment (TME) and non-genetic factors such as inflammation, smoking, and environmental exposures play crucial roles in promoting immune evasion. Understanding the timing and mechanisms of GIE, alongside microenvironmental influences, is crucial for improving early detection and developing more effective therapeutic interventions. This review highlights the implications of GIE in cancer development and immunotherapy resistance, and emphasizes the need for integrative approaches.