| Title: |
CD28/PD1 co-expression: dual impact on CD8+ T cells in peripheral blood and tumor tissue, and its significance in NSCLC patients' survival and ICB response |
| Authors: |
Palermo B.; Franzese O.; Frisullo G.; D'Ambrosio L.; Panetta M.; Campo G.; D'Andrea D.; Sperduti I.; De Nicola F.; Goeman F.; Gallina F.; Visca P.; Facciolo F.; Nistico P. |
| Contributors: |
Palermo, B.; Franzese, O.; Frisullo, G.; D'Ambrosio, L.; Panetta, M.; Campo, G.; D'Andrea, D.; Sperduti, I.; De Nicola, F.; Goeman, F.; Gallina, F.; Visca, P.; Facciolo, F.; Nistico, P. |
| Publisher Information: |
BioMed Central Ltd |
| Publication Year: |
2023 |
| Collection: |
Sapienza Università di Roma: CINECA IRIS |
| Subject Terms: |
CD28; CD8+ T cell; Immune Checkpoint Blockade; Non-small cell lung cancer; PD-1; Single-cell RNA-Seq; T-cell functionality |
| Description: |
Background: Immune checkpoint blockade (ICB) has significantly prolonged survival of non-small cell lung cancer (NSCLC) patients, although most patients develop mechanisms of resistance. Recently single-cell RNA-sequencing (scRNA-Seq) revealed a huge T-cell phenotypic and (dys)functional state variability. Accordingly, T-cell exhaustion is recognized as a functional adaptation, with a dynamic progression from a long-lived “pre-exhausted stem-like progenitor” to a “terminally exhausted” state. In this scenario it is crucial to understand the complex interplay between co-stimulatory and inhibitory molecules in CD8+ T-cell functionality. Methods: To gain a baseline landscape of the composition, functional states, and transcriptomic signatures predictive of prognosis, we analyzed CD8+ T-cell subsets characterized by the presence/absence of PD1 and CD28 from periphery, adjacent non-tumor tissue and tumor site of a cohort of treatment-naïve NSCLC patients, by integrated multiparametric flow cytometry, targeted multi-omic scRNA-seq analyses, and computational pipelines. Results: Despite the increased PD1 levels, an improved PD1+CD28+ T-cell polyfunctionality was observed with the transition from periphery to tumor site, associated with lack of TIGIT, TIM-3 and LAG-3, but not with Ag-experienced-marker CD11a. Differently from CD28+ T cells, the increased PD1 levels in the tumor were associated with reduced functionality in PD1+CD28− T cells. CD11ahigh, although expressed only in a small fraction of this subset, still sustained its functionality. Absence of TIGIT, TIM-3 and CTLA-4, alone or combined, was beneficial to CD28− T cells. Notably, we observed distinct TRM phenotypes in the different districts, with CD28+ T cells more capable of producing TGFβ in the periphery, potentially contributing to elevated CD103 levels. In contrast CD28− TRM mainly produced CXCL13 within the tumor. ScRNA-seq revealed 5 different clusters for each of the two subsets, with distinctive transcriptional profiles in the three districts. By ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/37898752; info:eu-repo/semantics/altIdentifier/wos/WOS:001092168000001; volume:42; issue:1; firstpage:1; lastpage:26; numberofpages:26; journal:JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH; https://hdl.handle.net/11573/1753690 |
| DOI: |
10.1186/s13046-023-02846-3 |
| Availability: |
https://hdl.handle.net/11573/1753690; https://doi.org/10.1186/s13046-023-02846-3 |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.D09314FD |
| Database: |
BASE |