TY - JOUR
T1 - OX40 agonism enhances PD-L1 checkpoint blockade by shifting the cytotoxic T cell differentiation spectrum
AU - van der Sluis, Tetje C.
AU - Beyrend, Guillaume
AU - van der Gracht, Esmé T.I.
AU - Abdelaal, Tamim
AU - Jochems, Simon P.
AU - Belderbos, Robert A.
AU - Wesselink, Thomas H.
AU - van Duikeren, Suzanne
AU - van Haften, Floortje J.
AU - Redeker, Anke
AU - Ouboter, Laura F.
AU - Beyranvand Nejad, Elham
AU - Camps, Marcel
AU - Franken, Kees L.M.C.
AU - Linssen, Margot M.
AU - Hohenstein, Peter
AU - de Miranda, Noel F.C.C.
AU - Mei, Hailiang
AU - Bins, Adriaan D.
AU - Haanen, John B.A.G.
AU - Aerts, Joachim G.
AU - Ossendorp, Ferry
AU - Arens, Ramon
N1 - Funding Information:
This research was funded by grants from the European Commission (Horizon 2020 MSCA grant under proposal number 675743 ; project acronym ISPIC), the Dutch Cancer Society (UL 2015–7817 to R.A.), and the LUMC Gisela Thier Fellowship (to T.C.v.d.S.).
Publisher Copyright:
© 2023 The Author(s)
PY - 2023/3/21
Y1 - 2023/3/21
N2 - Immune checkpoint therapy (ICT) has the power to eradicate cancer, but the mechanisms that determine effective therapy-induced immune responses are not fully understood. Here, using high-dimensional single-cell profiling, we interrogate whether the landscape of T cell states in the peripheral blood predict responses to combinatorial targeting of the OX40 costimulatory and PD-1 inhibitory pathways. Single-cell RNA sequencing and mass cytometry expose systemic and dynamic activation states of therapy-responsive CD4+ and CD8+ T cells in tumor-bearing mice with expression of distinct natural killer (NK) cell receptors, granzymes, and chemokines/chemokine receptors. Moreover, similar NK cell receptor-expressing CD8+ T cells are also detected in the blood of immunotherapy-responsive cancer patients. Targeting the NK cell and chemokine receptors in tumor-bearing mice shows the functional importance of these receptors for therapy-induced anti-tumor immunity. These findings provide a better understanding of ICT and highlight the use and targeting of dynamic biomarkers on T cells to improve cancer immunotherapy.
AB - Immune checkpoint therapy (ICT) has the power to eradicate cancer, but the mechanisms that determine effective therapy-induced immune responses are not fully understood. Here, using high-dimensional single-cell profiling, we interrogate whether the landscape of T cell states in the peripheral blood predict responses to combinatorial targeting of the OX40 costimulatory and PD-1 inhibitory pathways. Single-cell RNA sequencing and mass cytometry expose systemic and dynamic activation states of therapy-responsive CD4+ and CD8+ T cells in tumor-bearing mice with expression of distinct natural killer (NK) cell receptors, granzymes, and chemokines/chemokine receptors. Moreover, similar NK cell receptor-expressing CD8+ T cells are also detected in the blood of immunotherapy-responsive cancer patients. Targeting the NK cell and chemokine receptors in tumor-bearing mice shows the functional importance of these receptors for therapy-induced anti-tumor immunity. These findings provide a better understanding of ICT and highlight the use and targeting of dynamic biomarkers on T cells to improve cancer immunotherapy.
UR - http://www.scopus.com/inward/record.url?scp=85149643400&partnerID=8YFLogxK
U2 - 10.1016/j.xcrm.2023.100939
DO - 10.1016/j.xcrm.2023.100939
M3 - Article
C2 - 36796366
AN - SCOPUS:85149643400
SN - 2666-3791
VL - 4
JO - Cell Reports Medicine
JF - Cell Reports Medicine
IS - 3
M1 - 100939
ER -