The XCL1–XCR1 axis supports intestinal tissue residency and antitumor immunity
Authors:
- Amir FerryAFAmir Ferry
- Kianoosh M. MempelKMKianoosh M. Mempel
- Alexander MonellAMAlexander Monell
- Miguel Reina-CamposMRMiguel Reina-Campos
- Nicole E. ScharpingNSNicole E. Scharping
- Maximilian HeegMHMaximilian Heeg
- Kennidy K. TakeharaKTKennidy K. Takehara
- Shiruyeh SchokrpurSSShiruyeh Schokrpur
- Ning KuoNKNing Kuo
- Robert Saddawi-KonefkaRSRobert Saddawi-Konefka
- J. Silvio GutkindJGJ. Silvio Gutkind
- Ananda W. GoldrathAGAnanda W. Goldrath
- 22 January 2025
- journal article
- research article
- Published by Rockefeller University Press in Journal of Experimental Medicine
- Vol. 222 (2)
Abstract
Tissue-resident memory T cells (TRM) provide frontline protection against pathogens and emerging malignancies. Tumor-infiltrating lymphocytes (TIL) with TRM features are associated with improved clinical outcomes. However, the cellular interactions that program TRM differentiation and function are not well understood. Using murine genetic models and targeted spatial transcriptomics, we found that the CD8+ T cell–derived chemokine XCL1 is critical for TRM formation and conventional DC1 (cDC1) supported the positioning of intestinal CD8+ T cells during acute viral infection. In tumors, enforced Xcl1 expression by antigen-specific CD8+ T cells promoted intratumoral cDC1 accumulation and T cell persistence, leading to improved overall survival. Notably, analysis of human TIL and TRM revealed conserved expression of XCL1 and XCL2. Thus, we have shown that the XCL1–XCR1 axis plays a non-cell autonomous role in guiding intestinal CD8+ TRM spatial differentiation and tumor control.Keywords
Funding Information
- National Institutes of Health (R01AI179952)
- National Institutes of Health (R37AI067545)
- National Institutes of Health (R01AI072117)
- National Institutes of Health (R01AI150282)
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