Document Type
Article
Publication Date
11-8-2022
Publication Title
Nat Commun
Keywords
JMG, Humans, CD8-Positive T-Lymphocytes, Neutrophils, Colorectal Neoplasms, Lymphocytes, Tumor-Infiltrating
JAX Source
Nat Commun. 2022;13(1):6752
Volume
13
Issue
1
First Page
6752
ISSN
2041-1723
PMID
36347862
DOI
https://doi.org/10.1038/s41467-022-34467-3
Abstract
CD8+ T cells are a major prognostic determinant in solid tumors, including colorectal cancer (CRC). However, understanding how the interplay between different immune cells impacts on clinical outcome is still in its infancy. Here, we describe that the interaction of tumor infiltrating neutrophils expressing high levels of CD15 with CD8+ T effector memory cells (TEM) correlates with tumor progression. Mechanistically, stromal cell-derived factor-1 (CXCL12/ SDF-1) promotes the retention of neutrophils within tumors, increasing the crosstalk with CD8+ T cells. As a consequence of the contact-mediated inter- action with neutrophils, CD8+ T cells are skewed to produce high levels of GZMK, which in turn decreases E-cadherin on the intestinal epithelium and favors tumor progression. Overall, our results highlight the emergence of GZMKhigh CD8+ TEM in non-metastatic CRC tumors as a hallmark driven by the interaction with neutrophils, which could implement current patient stratifi- cation and be targeted by novel therapeutics.
Recommended Citation
Tiberti S,
Catozzi C,
Croci O,
Ballerini M,
Cagnina D,
Soriani C,
Scirgolea C,
Gong Z,
He J,
Macandog A,
Nabinejad A,
Nava Lauson C,
Quinte' A,
Bertalot G,
Petz W,
Ravenda S,
Licursi V,
Paci P,
Rasponi M,
Rotta L,
Fazio N,
Ren G,
Fumagalli-Romario U,
Schaefer M,
Campaner S,
Lugli E,
Nezi L,
Manzo T.
GZMK(high) CD8(+) T effector memory cells are associated with CD15(high) neutrophil abundance in non-metastatic colorectal tumors and predict poor clinical outcome Nat Commun. 2022;13(1):6752
Comments
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