Tumor immunotherapy: past, present, and future

Area of Science:

• Immunology and Cancer Research
• Translational Medicine

Background:

• Immunotherapy evolved from Jenner and Pasteur's work, shifting immunology to a reproducible science.
• The core principle of using pathogen characteristics to stimulate immune defenses remains central to modern immunotherapy.

Purpose of the Study:

• To review the origins and development of immunotherapy.
• To propose a "synergistic functional loop" model of tumor immunity.
• To present a hierarchical efficacy pyramid for tumor immunotherapy.

Main Methods:

• Systematic review of immunotherapy origins and development.
• Analysis of successful and failed clinical trials.
• Comparative assessment of various immunotherapeutic techniques based on efficacy, safety, and potential.

Main Results:

• A "synergistic functional loop" model comprising antigen-sensing, cytotoxic-killing, immunoregulatory, and tumor-educating loops is proposed.
• A three-tiered "efficacy pyramid" (local remodeling, systemic activation, cell killing) is outlined for tumor immunotherapy.
• Factors influencing immunotherapy success (tumor type, markers, microenvironment, patient status) and failure (complexity, heterogeneity, resistance) were identified.

Conclusions:

• Effective immunotherapy requires consideration of tumor-specific and patient-specific factors.
• Challenges in immunotherapy include mechanism complexity, tumor heterogeneity, and immune evasion.
• Novel perspectives are proposed to address current challenges in the field of tumor immunotherapy.