TY - JOUR
T1 - The interaction of CD4+ helper T cells with dendritic cells shapes the tumor microenvironment and immune checkpoint blockade response
AU - Cohen, Merav
AU - Giladi, Amir
AU - Barboy, Oren
AU - Hamon, Pauline
AU - Li, Baoguo
AU - Zada, Mor
AU - Gurevich-Shapiro, Anna
AU - Beccaria, Cristian Gabriel
AU - David, Eyal
AU - Maier, Barbara B.
AU - Buckup, Mark
AU - Kamer, Iris
AU - Deczkowska, Aleksandra
AU - Le Berichel, Jessica
AU - Bar, Jair
AU - Iannacone, Matteo
AU - Tanay, Amos
AU - Merad, Miriam
AU - Amit, Ido
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2022/3
Y1 - 2022/3
N2 - Despite their key regulatory role and therapeutic potency, the molecular signatures of interactions between T cells and antigen-presenting myeloid cells within the tumor microenvironment remain poorly characterized. Here, we systematically characterize these interactions using RNA sequencing of physically interacting cells (PIC-seq) and find that CD4+PD-1+CXCL13+ T cells are a major interacting hub with antigen-presenting cells in the tumor microenvironment of human non-small cell lung carcinoma. We define this clonally expanded, tumor-specific and conserved T-cell subset as T-helper tumor (Tht) cells. Reconstitution of Tht cells in vitro and in an ovalbumin-specific αβ TCR CD4+ T-cell mouse model, shows that the Tht program is primed in tumor-draining lymph nodes by dendritic cells presenting tumor antigens, and that their function is important for harnessing the antitumor response of anti-PD-1 treatment. Our molecular and functional findings support the modulation of Tht–dendritic cell interaction checkpoints as a major interventional strategy in immunotherapy.
AB - Despite their key regulatory role and therapeutic potency, the molecular signatures of interactions between T cells and antigen-presenting myeloid cells within the tumor microenvironment remain poorly characterized. Here, we systematically characterize these interactions using RNA sequencing of physically interacting cells (PIC-seq) and find that CD4+PD-1+CXCL13+ T cells are a major interacting hub with antigen-presenting cells in the tumor microenvironment of human non-small cell lung carcinoma. We define this clonally expanded, tumor-specific and conserved T-cell subset as T-helper tumor (Tht) cells. Reconstitution of Tht cells in vitro and in an ovalbumin-specific αβ TCR CD4+ T-cell mouse model, shows that the Tht program is primed in tumor-draining lymph nodes by dendritic cells presenting tumor antigens, and that their function is important for harnessing the antitumor response of anti-PD-1 treatment. Our molecular and functional findings support the modulation of Tht–dendritic cell interaction checkpoints as a major interventional strategy in immunotherapy.
UR - http://www.scopus.com/inward/record.url?scp=85125541804&partnerID=8YFLogxK
U2 - 10.1038/s43018-022-00338-5
DO - 10.1038/s43018-022-00338-5
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C2 - 35241835
AN - SCOPUS:85125541804
SN - 2662-1347
VL - 3
SP - 303
EP - 317
JO - Nature Cancer
JF - Nature Cancer
IS - 3
ER -