Wislez, M. | Search bioRxiv

bioRxiv2024

Differential predictive value of resident memory CD8+T cell subpopulations in non-small-cell lung cancer patients treated by immunotherapy

A high density of resident memory T cells (TRM) in tumors correlates with improved clinical outcomes in immunotherapy-treated patients. However, in preclinical models, only some subpopulations of TRM are associated with cancer vaccine efficacy. We identified two main TRM subpopulations in tumor-infiltrating lymphocytes derived from non-small cell lung cancer (NSCLC) patients: one co-expressing CD103 and CD49a (DP), and the other expressing only CD49a (MP); both exhibiting additional TRM surface markers like CD69. DP TRM exhibited greater functionality compared to MP TRM. Analysis of T-cell receptor (TCR) repertoire and of the stemness marker TCF-1 revealed shared TCRs between populations, with the MP subset appearing more progenitor-like phenotype. In two NSCLC patient cohorts, only DP TRM predicted PD-1 blockade response. Multivariate analysis, including various biomarkers (CD8, TCF1+CD8+T cells, and PD-L1) associated with responses to anti-PD(L)1, showed that only intra-tumoral infiltration by DP TRM remained significant. This study highlights the non-equivalence of TRM populations and emphasizes the importance of distinguishing between them to better define their role in antitumor immunity and as a biomarker of response to immunotherapy.

immunology↗

bioRxiv2023

Biased cell adhesion organizes a circuit for visual motion integration

Layer specific computations in the brain rely on neuronal processes establishing synaptic connections with specific partners in distinct laminae. In the Drosophila lobula plate neuropile, the axons of the four subtypes of T4 and T5 visual motion direction-selective neurons segregate into four layers, based on their directional preference, and form synapses with distinct subsets of postsynaptic neurons. Four bi-stratified inhibitory lobula plate intrinsic cells exhibit a consistent synaptic pattern, receiving excitatory T4/T5 inputs in one layer, and conveying inhibitory signals to an adjacent layer. This layered arrangement establishes motion opponency. Here, we identify layer-specific expression of different receptor-ligand pairs belonging to the Beat and Side families of Cell Adhesion Molecules (CAMs) between T4/T5 neurons and their postsynaptic partners. Genetic analysis reveals that Beat/Side mediated interactions are required to restrict T4/T5 axonal innervation to a single layer. We propose that Beat/Side contribute to synaptic specificity by biasing adhesion between synaptic partners before synaptogenesis.

developmental biology↗