| RRC ID |
86981
|
| Author |
Steele MM, Jaiswal A, Delclaux I, Dryg ID, Murugan D, Femel J, Son S, du Bois H, Hill C, Leachman SA, Chang YH, Coussens LM, Anandasabapathy N, Lund AW.
|
| Title |
T cell egress via lymphatic vessels is tuned by antigen encounter and limits tumor control.
|
| Journal |
Nat Immunol
|
| Abstract |
Antigen-specific CD8+ T cell accumulation in tumors is a prerequisite for effective immunotherapy, and yet the mechanisms of lymphocyte transit are not well defined. Here we show that tumor-associated lymphatic vessels control T cell exit from tumors via the chemokine CXCL12, and intratumoral antigen encounter tunes CXCR4 expression by effector CD8+ T cells. Only high-affinity antigen downregulates CXCR4 and upregulates the CXCL12 decoy receptor, ACKR3, thereby reducing CXCL12 sensitivity and promoting T cell retention. A diverse repertoire of functional tumor-specific CD8+ T cells, therefore, exit the tumor, which limits the pool of CD8+ T cells available to exert tumor control. CXCR4 inhibition or loss of lymphatic-specific CXCL12 boosts T cell retention and enhances tumor control. These data indicate that strategies to limit T cell egress might be an approach to boost the quantity and quality of intratumoral T cells and thereby response to immunotherapy.
|
| Volume |
24(4)
|
| Pages |
664-675
|
| Published |
2023-4-1
|
| DOI |
10.1038/s41590-023-01443-y
|
| PII |
10.1038/s41590-023-01443-y
|
| PMID |
36849745
|
| PMC |
PMC10998279
|
| MeSH |
CD8-Positive T-Lymphocytes
Humans
Immunotherapy
Lymphatic Vessels* / metabolism
Neoplasms* / pathology
Neoplasms* / therapy
Receptors, CXCR4 / metabolism
|
| IF |
20.479
|
| Resource |
| Mice |
RBRC05737 |
