Innate immunity in tumors: From mechanisms to therapeutics

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Current cancer immunotherapies primarily target the adaptive immune system, showing limited clinical success.
• Innate immunity, the body's initial defense, plays a crucial role in directly eliminating tumor cells and initiating adaptive immune responses.
• The tumor microenvironment (TME) often suppresses innate immune cell functions, hindering effective anti-tumor activity.

Purpose of the Study:

• To review the multifaceted roles of innate immune cells within the TME.
• To examine the mechanisms by which the TME suppresses innate immunity.
• To highlight emerging therapeutic strategies aimed at enhancing innate immune responses for improved cancer immunotherapy.

Main Methods:

• Review of scientific literature on innate immunity in cancer.
• Analysis of the functions and plasticity of key innate immune cells (NK cells, DCs, macrophages, etc.) in the TME.
• Examination of TME-mediated suppressive mechanisms (immune checkpoints, metabolic reprogramming, cytokines, ECM, etc.).
• Identification and discussion of novel therapeutic approaches, including engineered cellular therapies (CAR-NK, CAR-macrophages) and macromolecular strategies.

Main Results:

• Innate immune cells exhibit both anti-tumor and pro-tumorigenic functions within the TME.
• Multiple TME-associated factors significantly impair innate immune cell activity and anti-tumor efficacy.
• Engineered cellular therapies and macromolecular strategies show potential to reverse TME-induced immunosuppression and enhance anti-tumor responses.

Conclusions:

• Enhancing innate immunity is critical for converting 'cold' tumors into 'hot' tumors responsive to immunotherapy.
• Future advancements require integrating multiomics, optimizing engineered therapies, and developing combination strategies.
• Leveraging both innate and adaptive immunity holds the key to more effective cancer immunotherapy.