Adaptive resistance in cancer immunotherapy

Area of Science:

• Immunology
• Oncology
• Cancer Research

Background:

• Cancer immunotherapy has revolutionized oncology but benefits only a subset of patients.
• Adaptive resistance, characterized by T-cell exhaustion, is a major limitation.
• This resistance manifests as on-treatment progression or post-treatment relapse.

Purpose of the Study:

• To synthesize current knowledge on adaptive resistance to cancer immunotherapy.
• To emphasize the role of dysfunctional T-cell responses in resistance.
• To evaluate emerging strategies for overcoming resistance.

Main Methods:

• Review of current literature on cancer immunoediting and antitumor immune memory (AIM).
• Analysis of T-cell exhaustion mechanisms within the tumor microenvironment (TME).
• Systematic analysis of cellular and molecular drivers of T-cell dysfunction.

Main Results:

• T-cell exhaustion undermines immunotherapy efficacy, leading to distinct resistance patterns.
• Dysfunctional T cells in the TME and lymph nodes drive insufficient tumor killing or failure to establish durable AIM.
• Current immunotherapy regimens have limitations in overcoming adaptive resistance.

Conclusions:

• Adaptive resistance is driven by progressive T-cell exhaustion.
• Understanding T-cell dysfunction is crucial for developing next-generation immunotherapies.
• Emerging strategies aim to rejuvenate exhausted T cells and overcome resistance.