T-cell Priming by High-Avidity Neoantigens in Lymph Nodes Augments Adoptive Immunotherapy

Area of Science:

• Immunology
• Cancer Biology
• Cellular Therapy

Background:

• Adoptive T cell therapy shows promise for solid tumors.
• The impact of tumor antigen avidity on T cell function is not fully understood.

Purpose of the Study:

• To investigate how tumor antigen avidity influences CD8+ T cell differentiation and anti-tumor immunity.
• To compare the efficacy of T cells responding to low-avidity vs. high-avidity antigens.

Main Methods:

• Comparative analysis of T cell responses to melanoma expressing low-avidity antigen vs. high-avidity neoantigen.
• Kinetic profiling of T cell differentiation and function in host tissues.
• Assessment of anti-tumor activity and immune memory in vivo.

Main Results:

• High-avidity neoantigen expression induced robust activation, effector function, and persistence of transferred T cells.
• Tumor regression and long-term protective immunity were observed with high-avidity neoantigens.
• Early lymph node trafficking of T cells was essential for effective adoptive cell therapy.
• Stem-memory T cells showed comparable efficacy to naive T cells against high-avidity tumors.

Conclusions:

• Tumor antigen avidity significantly shapes T cell fate and anti-tumor responses.
• Lymph node trafficking is a critical factor for successful adoptive cell therapy targeting high-avidity neoantigens.
• Understanding antigen avidity can optimize T cell-based cancer immunotherapies.