Oncological immunotherapy: immunological foundations, toxicity, resistance mechanisms, and difficulty of access

Abstract

Objective: To analyze the mechanisms of tumor immune evasion and the therapeutic impact of immune checkpoint inhibitors (ICIs) in the treatment of solid and hematological neoplasms, discussing clinical challenges and access barriers. Literature review: Cancer utilizes mechanisms such as the hypoxia–HIF-1α–CD73 axis and PD-L1 overexpression to create an immunosuppressive microenvironment composed of Tregs, MDSCs, and M2 macrophages. Immunotherapy with anti-CTLA-4, anti-PD-1, and anti-PD-L1 antibodies restores T-lymphocyte cytotoxicity, presenting durable responses in tumors such as melanoma and lung carcinoma. However, efficacy is limited by tumor resistance and the occurrence of immune-related adverse events (irAEs) in organs such as the lungs and gastrointestinal tract, in addition to global economic disparities that restrict access to therapies in low- and middle-income countries. Final considerations: Immunotherapy represents a milestone in modern oncology, although its consolidation depends on the identification of predictive biomarkers and strategies that minimize tumor resistance. The study highlights the need for public policies to democratize access and rigorous clinical management of adverse effects to ensure patient safety.