Tissue-resident memory and circulating T cells are early responders to pre-surgical cancer immunotherapy

Area of Science:

• Immunology
• Oncology
• Cancer immunotherapy

Background:

• Neoadjuvant immune checkpoint blockade demonstrates clinical promise in various cancers.
• Understanding early immune cell dynamics is crucial for optimizing immunotherapy strategies.

Purpose of the Study:

• To characterize the early kinetics of tumor-infiltrating and circulating immune cells in oral cancer patients receiving neoadjuvant anti-PD-1 or anti-PD-1/CTLA-4 therapy.
• To identify immune cell signatures associated with treatment response.

Main Methods:

• Analysis of tumor-infiltrating and circulating immune cells from oral cancer patients in a clinical trial (NCT02919683).
• Assessment of CD8 T cell clon expansion, memory programs, cytotoxicity, and self-antigen recognition.
• Correlation of peripheral blood immune cell frequencies with intra-tumoral pathological response.

Main Results:

• Clonally expanded tumor-infiltrating CD8 T cells exhibited pre-existing tissue-resident memory and cytotoxicity programs.
• Responding patients showed T cell recognition of self-antigens, including MAGEA1.
• Systemic immune response included expansion of activated T cells with shared clonotypes, both pre-existing and emergent.
• Frequency of activated blood CD8 T cells (PD-1+ KLRG1-) correlated with pathological response.

Conclusions:

• Neoadjuvant checkpoint blockade effectively induces local and systemic anti-tumor immunity.
• Early immune cell kinetics, including specific peripheral T cell populations, are predictive of treatment outcomes.
• These findings support the role of neoadjuvant immunotherapy in enhancing tumor-specific immune responses.