| Title: |
ICAM-1 on cDC1 promotes the survival of stem-like memory CD8 T cells generated in tumor draining lymph nodes |
| Authors: |
Levi, Nehora; Kozlovski, Stav; Kizner, Marina; Biton, Moshe; Alon, Ronen |
| Source: |
South East European Journal of Immunology; Vol. 8 No. CITIM (2025): SEE J Immunol; 028 ; 1857-9388 ; 10.3889/seejim.2025.8.CITIM |
| Publisher Information: |
Scientific Foundation SPIROSKI, Skopje, Republic of Macedonia |
| Publication Year: |
2025 |
| Subject Terms: |
Dendritic Cells (DCs); ICAM-1; CD8 T Cells; Tumor Antigen Cross-Presentation; T-stem-like central memory T cells |
| Description: |
Dendritic cells (DCs) cross-present tumor antigens to cognate T cells in tumor-draining lymph nodes (TdLNs). ICAM-1 is a key adhesion molecule involved in the formation of diverse cell-cell contacts between immune cells as well as blood vessels and stromal cells. We have recently found that ICAM-1 expressed by lymph node DCs can stabilize antigen-dependent contacts with naïve CD8 T cells but is dispensable for CD8 T cell differentiation and proliferation into effector and memory lymphocytes generated in various models of vaccination and virus infections. To follow the role of DC ICAM-1 in CD8 proliferation and differentiation triggered by tumor expressed neoantigens, we orthotopically implanted breast cancer E0771 cells expressing the model OVA neoantigen in immunocompetent mice conditionally deleted of ICAM-1 expression in all CD11c expressing -conventional DCs (cDCs), monocyte derived DCs (mDCs) and pDCs. Strikingly, in contrast to viral challenges, the tumor challenge drove naïve tumor-antigen specific CD8 differentiation almost exclusively into T-stem-like central memory T cells (TSL) with high expression of L-selectin (CD62L), PD-1, and the transcription factor TCF-1 implicated in T cell stemness and proliferative potential. Early CD8 activation and differentiation into these central memory T cells remained normal in these mice. This indicated that tumor antigen transfer by migratory DCs to lymph node DCs and its initial cross presentation to naïve T cells do not require ICAM-1 expression by all types of DCs. Furthermore, deletion of ICAM-1 selectively in XCR1 conventional type 1 dendritic cells(cDC1), specialized in tumor antigen uptake and cross priming of tumor specific T cells in tumor draining lymph nodes, did not impair early tumor specific CD8 activation and differentiation. Nevertheless, the maintenance of resident self-renewing stem-like tumor specific CD8 memory cells in the tumor draining lymph nodes was diminished in the absence of ICAM-1 expression by cDC1. We currently explore the possibility ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://seejim.eu/index.php/seejim/article/view/6089/5558; https://seejim.eu/index.php/seejim/article/view/6089 |
| DOI: |
10.3889/seejim.2025.6089 |
| Availability: |
https://seejim.eu/index.php/seejim/article/view/6089; https://doi.org/10.3889/seejim.2025.6089 |
| Rights: |
Copyright (c) 2025 Nehora Levi, Stav Kozlovski, Marina Kizner, Moshe Biton, Ronen Alon ; http://creativecommons.org/licenses/by-nc/4.0 |
| Accession Number: |
edsbas.D74B20F |
| Database: |
BASE |