PET-based immunomapping of intratumoral CD4⁺ cells to monitor acquired resistance to checkpoint inhibitors.

ABSTRACT: CD4⁺ T cells are crucial in shaping response and resistance to immunotherapy. To enhance our understanding of their multifaceted functions, we developed copper-64-radiolabeled nanobodies targeting the human CD4 receptor (⁶⁴Cu-CD4-Nb1) for positron emission tomography (PET). In human CD4-receptor knock-in mice, ⁶⁴Cu-CD4-Nb1 specifically accumulated in different orthotopic tumors, correlating with histological CD4⁺ cell densities. Based on intratumoral CD4⁺ cell distribution patterns within the core and periphery, we distinguished responders to combined αPD-1/4-1BB antibodies early on-treatment. CD4-PET identified resistance to αPD-1 monotherapy, which was mitigated by adding regulatory T cell-depleting α4-1BB antibodies. Patients with e

SUBMITTER: Pezzana S 

PROVIDER: S-EPMC12190014 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature