Immune checkpoint therapy for solid tumours: clinical dilemmas and future trends

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Immune-checkpoint inhibitors (ICIs) targeting CTLA-4, PD-1, and PD-L1 have revolutionized cancer treatment, with LAG-3 inhibitors now also in clinical use.
• Despite significant efficacy in melanoma and non-small cell lung cancer (NSCLC), ICIs face limitations in solid tumors, including non-specific indications, immune-related adverse events, and complex resistance mechanisms.

Purpose of the Study:

• To analyze the current challenges and future prospects of immune-checkpoint inhibitor therapy.
• To review the mechanisms, efficacy, and safety of existing and novel ICIs across various tumor types.
• To discuss the role of predictive biomarkers and diagnostic techniques in optimizing ICI treatment.

Main Methods:

• Literature review of immune checkpoint targets, mechanisms, and clinical trial data.
• Analysis of associations between ICIs, tumor mutation burden, and immune resistance pathways.
• Examination of efficacy data for classical and novel ICI targets in different cancers.

Main Results:

• ICIs have demonstrated dramatic efficacy in specific cancers but face barriers in broader solid tumor application.
• Emerging strategies like combination therapies, oncolytic viruses, mRNA vaccines, and nano-delivery systems show promise.
• Predictive biomarkers and advanced diagnostics are crucial for patient selection and treatment efficacy.

Conclusions:

• Addressing the limitations of ICIs requires a multifaceted approach, including novel therapeutic strategies and improved patient stratification.
• Further research into immune regulatory networks and resistance mechanisms is essential for enhancing ICI effectiveness.
• Accurate patient triage using predictive biomarkers will be key to maximizing the benefits of ICI therapy.