BibTex format
@article{Patin:2024:10.1038/s41467-024-51236-6,
author = {Patin, EC and Nenclares, P and Chan, Wah Hak C and Dillon, MT and Patrikeev, A and McLaughlin, M and Grove, L and Foo, S and Soliman, H and Barata, JP and Marsden, J and Baldock, H and Gkantalis, J and Roulstone, V and Kyula, J and Burley, A and Hubbard, L and Pedersen, M and Smith, SA and Clancy-Thompson, E and Melcher, AA and Ono, M and Rullan, A and Harrington, KJ},
doi = {10.1038/s41467-024-51236-6},
journal = {Nat Commun},
title = {Sculpting the tumour microenvironment by combining radiotherapy and ATR inhibition for curative-intent adjuvant immunotherapy.},
url = {http://dx.doi.org/10.1038/s41467-024-51236-6},
volume = {15},
year = {2024}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - The combination of radiotherapy/chemoradiotherapy and immune checkpoint blockade can result in poor outcomes in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Here, we show that combining ATR inhibition (ATRi) with radiotherapy (RT) increases the frequency of activated NKG2A+PD-1+ T cells in animal models of HNSCC. Compared with the ATRi/RT treatment regimen alone, the addition of simultaneous NKG2A and PD-L1 blockade to ATRi/RT, in the adjuvant, post-radiotherapy setting induces a robust antitumour response driven by higher infiltration and activation of cytotoxic T cells in the tumour microenvironment. The efficacy of this combination relies on CD40/CD40L costimulation and infiltration of activated, proliferating memory CD8+ and CD4+ T cells with persistent or new T cell receptor (TCR) signalling, respectively. We also observe increased richness in the TCR repertoire and emergence of numerous and large TCR clonotypes that cluster based on antigen specificity in response to NKG2A/PD-L1/ATRi/RT. Collectively, our data point towards potential combination approaches for the treatment of HNSCC.
AU - Patin,EC
AU - Nenclares,P
AU - Chan,Wah Hak C
AU - Dillon,MT
AU - Patrikeev,A
AU - McLaughlin,M
AU - Grove,L
AU - Foo,S
AU - Soliman,H
AU - Barata,JP
AU - Marsden,J
AU - Baldock,H
AU - Gkantalis,J
AU - Roulstone,V
AU - Kyula,J
AU - Burley,A
AU - Hubbard,L
AU - Pedersen,M
AU - Smith,SA
AU - Clancy-Thompson,E
AU - Melcher,AA
AU - Ono,M
AU - Rullan,A
AU - Harrington,KJ
DO - 10.1038/s41467-024-51236-6
PY - 2024///
TI - Sculpting the tumour microenvironment by combining radiotherapy and ATR inhibition for curative-intent adjuvant immunotherapy.
T2 - Nat Commun
UR - http://dx.doi.org/10.1038/s41467-024-51236-6
UR - https://www.ncbi.nlm.nih.gov/pubmed/39134540
VL - 15
ER -