Augmenting Immunotherapy Impact by Lowering Tumor TNF Cytotoxicity Threshold

David W. Vredevoogd, Thomas Kuilman, Maarten A. Ligtenberg, Julia Boshuizen, Kelly E. Stecker, Beaunelle de Bruijn, Oscar Krijgsman, Xinyao Huang, Juliana C. N. Kenski, Ruben Lacroix, Riccardo Mezzadra, Raquel Gomez-Eerland, Mete Yildiz, Ilknur Dagidir, Georgi Apriamashvili, Nordin Zandhuis, Vincent van der Noort, Nils L. Visser, Christian U. Blank, Maarten Altelaar & 2 others Ton N. Schumacher, Daniel S. Peeper

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

New opportunities are needed to increase immune checkpoint blockade (ICB) impact for cancer patients. A genome-wide CRISPR/Cas9 screen uncovered several hits in the TNF pathway sensitizing tumor cells to T cell elimination. TNF antitumor activity was generally limited in tumors at baseline and in ICB non-responders, correlating with its low abundance. Selective inactivation of TNF signaling lowered melanoma and lung cancer thresholds to low TNF levels, thereby increasing tumor susceptibility to T cell attack and augmenting benefit from anti-PD-1 treatment.
Original languageEnglish
Pages (from-to)585-599.e15
JournalCell
Volume178
Issue number3
DOIs
Publication statusPublished - 25 Jul 2019
Externally publishedYes

Cite this

Vredevoogd, D. W., Kuilman, T., Ligtenberg, M. A., Boshuizen, J., Stecker, K. E., de Bruijn, B., ... Peeper, D. S. (2019). Augmenting Immunotherapy Impact by Lowering Tumor TNF Cytotoxicity Threshold. Cell, 178(3), 585-599.e15. https://doi.org/10.1016/j.cell.2019.06.014
Vredevoogd, David W. ; Kuilman, Thomas ; Ligtenberg, Maarten A. ; Boshuizen, Julia ; Stecker, Kelly E. ; de Bruijn, Beaunelle ; Krijgsman, Oscar ; Huang, Xinyao ; Kenski, Juliana C. N. ; Lacroix, Ruben ; Mezzadra, Riccardo ; Gomez-Eerland, Raquel ; Yildiz, Mete ; Dagidir, Ilknur ; Apriamashvili, Georgi ; Zandhuis, Nordin ; van der Noort, Vincent ; Visser, Nils L. ; Blank, Christian U. ; Altelaar, Maarten ; Schumacher, Ton N. ; Peeper, Daniel S. / Augmenting Immunotherapy Impact by Lowering Tumor TNF Cytotoxicity Threshold. In: Cell. 2019 ; Vol. 178, No. 3. pp. 585-599.e15.
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abstract = "New opportunities are needed to increase immune checkpoint blockade (ICB) impact for cancer patients. A genome-wide CRISPR/Cas9 screen uncovered several hits in the TNF pathway sensitizing tumor cells to T cell elimination. TNF antitumor activity was generally limited in tumors at baseline and in ICB non-responders, correlating with its low abundance. Selective inactivation of TNF signaling lowered melanoma and lung cancer thresholds to low TNF levels, thereby increasing tumor susceptibility to T cell attack and augmenting benefit from anti-PD-1 treatment.",
author = "Vredevoogd, {David W.} and Thomas Kuilman and Ligtenberg, {Maarten A.} and Julia Boshuizen and Stecker, {Kelly E.} and {de Bruijn}, Beaunelle and Oscar Krijgsman and Xinyao Huang and Kenski, {Juliana C. N.} and Ruben Lacroix and Riccardo Mezzadra and Raquel Gomez-Eerland and Mete Yildiz and Ilknur Dagidir and Georgi Apriamashvili and Nordin Zandhuis and {van der Noort}, Vincent and Visser, {Nils L.} and Blank, {Christian U.} and Maarten Altelaar and Schumacher, {Ton N.} and Peeper, {Daniel S.}",
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Vredevoogd, DW, Kuilman, T, Ligtenberg, MA, Boshuizen, J, Stecker, KE, de Bruijn, B, Krijgsman, O, Huang, X, Kenski, JCN, Lacroix, R, Mezzadra, R, Gomez-Eerland, R, Yildiz, M, Dagidir, I, Apriamashvili, G, Zandhuis, N, van der Noort, V, Visser, NL, Blank, CU, Altelaar, M, Schumacher, TN & Peeper, DS 2019, 'Augmenting Immunotherapy Impact by Lowering Tumor TNF Cytotoxicity Threshold' Cell, vol. 178, no. 3, pp. 585-599.e15. https://doi.org/10.1016/j.cell.2019.06.014

Augmenting Immunotherapy Impact by Lowering Tumor TNF Cytotoxicity Threshold. / Vredevoogd, David W.; Kuilman, Thomas; Ligtenberg, Maarten A.; Boshuizen, Julia; Stecker, Kelly E.; de Bruijn, Beaunelle; Krijgsman, Oscar; Huang, Xinyao; Kenski, Juliana C. N.; Lacroix, Ruben; Mezzadra, Riccardo; Gomez-Eerland, Raquel; Yildiz, Mete; Dagidir, Ilknur; Apriamashvili, Georgi; Zandhuis, Nordin; van der Noort, Vincent; Visser, Nils L.; Blank, Christian U.; Altelaar, Maarten; Schumacher, Ton N.; Peeper, Daniel S.

In: Cell, Vol. 178, No. 3, 25.07.2019, p. 585-599.e15.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Augmenting Immunotherapy Impact by Lowering Tumor TNF Cytotoxicity Threshold

AU - Vredevoogd, David W.

AU - Kuilman, Thomas

AU - Ligtenberg, Maarten A.

AU - Boshuizen, Julia

AU - Stecker, Kelly E.

AU - de Bruijn, Beaunelle

AU - Krijgsman, Oscar

AU - Huang, Xinyao

AU - Kenski, Juliana C. N.

AU - Lacroix, Ruben

AU - Mezzadra, Riccardo

AU - Gomez-Eerland, Raquel

AU - Yildiz, Mete

AU - Dagidir, Ilknur

AU - Apriamashvili, Georgi

AU - Zandhuis, Nordin

AU - van der Noort, Vincent

AU - Visser, Nils L.

AU - Blank, Christian U.

AU - Altelaar, Maarten

AU - Schumacher, Ton N.

AU - Peeper, Daniel S.

PY - 2019/7/25

Y1 - 2019/7/25

N2 - New opportunities are needed to increase immune checkpoint blockade (ICB) impact for cancer patients. A genome-wide CRISPR/Cas9 screen uncovered several hits in the TNF pathway sensitizing tumor cells to T cell elimination. TNF antitumor activity was generally limited in tumors at baseline and in ICB non-responders, correlating with its low abundance. Selective inactivation of TNF signaling lowered melanoma and lung cancer thresholds to low TNF levels, thereby increasing tumor susceptibility to T cell attack and augmenting benefit from anti-PD-1 treatment.

AB - New opportunities are needed to increase immune checkpoint blockade (ICB) impact for cancer patients. A genome-wide CRISPR/Cas9 screen uncovered several hits in the TNF pathway sensitizing tumor cells to T cell elimination. TNF antitumor activity was generally limited in tumors at baseline and in ICB non-responders, correlating with its low abundance. Selective inactivation of TNF signaling lowered melanoma and lung cancer thresholds to low TNF levels, thereby increasing tumor susceptibility to T cell attack and augmenting benefit from anti-PD-1 treatment.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/31303383

U2 - 10.1016/j.cell.2019.06.014

DO - 10.1016/j.cell.2019.06.014

M3 - Article

VL - 178

SP - 585-599.e15

JO - Cell

JF - Cell

SN - 0092-8674

IS - 3

ER -

Vredevoogd DW, Kuilman T, Ligtenberg MA, Boshuizen J, Stecker KE, de Bruijn B et al. Augmenting Immunotherapy Impact by Lowering Tumor TNF Cytotoxicity Threshold. Cell. 2019 Jul 25;178(3):585-599.e15. https://doi.org/10.1016/j.cell.2019.06.014