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Citations to this article

Memory T cell–driven differentiation of naive cells impairs adoptive immunotherapy
Christopher A. Klebanoff, … , Richard M. Siegel, Nicholas P. Restifo
Christopher A. Klebanoff, … , Richard M. Siegel, Nicholas P. Restifo
Published December 14, 2015
Citation Information: J Clin Invest. 2016;126(1):318-334. https://doi.org/10.1172/JCI81217.
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Research Article Immunology Oncology Article has an altmetric score of 28

Memory T cell–driven differentiation of naive cells impairs adoptive immunotherapy

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Abstract

Adoptive cell transfer (ACT) of purified naive, stem cell memory, and central memory T cell subsets results in superior persistence and antitumor immunity compared with ACT of populations containing more-differentiated effector memory and effector T cells. Despite a clear advantage of the less-differentiated populations, the majority of ACT trials utilize unfractionated T cell subsets. Here, we have challenged the notion that the mere presence of less-differentiated T cells in starting populations used to generate therapeutic T cells is sufficient to convey their desirable attributes. Using both mouse and human cells, we identified a T cell–T cell interaction whereby antigen-experienced subsets directly promote the phenotypic, functional, and metabolic differentiation of naive T cells. This process led to the loss of less-differentiated T cell subsets and resulted in impaired cellular persistence and tumor regression in mouse models following ACT. The T memory–induced conversion of naive T cells was mediated by a nonapoptotic Fas signal, resulting in Akt-driven cellular differentiation. Thus, induction of Fas signaling enhanced T cell differentiation and impaired antitumor immunity, while Fas signaling blockade preserved the antitumor efficacy of naive cells within mixed populations. These findings reveal that T cell subsets can synchronize their differentiation state in a process similar to quorum sensing in unicellular organisms and suggest that disruption of this quorum-like behavior among T cells has potential to enhance T cell–based immunotherapies.

Authors

Christopher A. Klebanoff, Christopher D. Scott, Anthony J. Leonardi, Tori N. Yamamoto, Anthony C. Cruz, Claudia Ouyang, Madhu Ramaswamy, Rahul Roychoudhuri, Yun Ji, Robert L. Eil, Madhusudhanan Sukumar, Joseph G. Crompton, Douglas C. Palmer, Zachary A. Borman, David Clever, Stacy K. Thomas, Shashankkumar Patel, Zhiya Yu, Pawel Muranski, Hui Liu, Ena Wang, Francesco M. Marincola, Alena Gros, Luca Gattinoni, Steven A. Rosenberg, Richard M. Siegel, Nicholas P. Restifo

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2009 Total
Citations: 6 13 11 20 20 21 13 21 19 11 1 1 157
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2016 (11)

Title and authors Publication Year
Generation of clinical-grade CD19-specific CAR-modified CD8+ memory stem cells for the treatment of human B-cell malignancies
M Sabatino, J Hu, M Sommariva, S Gautam, V Fellowes, JD Hocker, S Dougherty, H Qin, CA Klebanoff, TJ Fry, RE Gress, JN Kochenderfer, DF Stroncek, Y Ji, L Gattinoni
Blood 2016
Role of memory T cell subsets for adoptive immunotherapy
DH Busch, SP Fräßle, D Sommermeyer, VR Buchholz, SR Riddell
Seminars in Immunology 2016
Regulatory circuits of T cell function in cancer
DE Speiser, PC Ho, G Verdeil
Nature Reviews Immunology 2016
Interleukin-15 enhances the proliferation, stimulatory phenotype, and antitumor effector functions of human gamma delta T cells
HH van Acker, S Anguille, Y Willemen, JM van Bergh, ZN Berneman, E Lion, EL Smits, VF van Tendeloo
Journal of Hematology & Oncology 2016
Immunology: Channelling potassium to fight cancer
KG Chandy, RS Norton
Nature 2016
Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells
LV Hurton, H Singh, AM Najjar, KC Switzer, T Mi, S Maiti, S Olivares, B Rabinovich, H Huls, MA Forget, V Datar, P Kebriaei, DA Lee, RE Champlin, LJ Cooper
Proceedings of the National Academy of Sciences 2016
Driving gene-engineered T cell immunotherapy of cancer
LA Johnson, CH June
Cell Research 2016
Cell-Intrinsic Barriers of T Cell-Based Immunotherapy
HE Ghoneim, AE Zamora, PG Thomas, BA Youngblood
Trends in Molecular Medicine 2016
A Rapid Cell Expansion Process for Production of Engineered Autologous CAR-T Cell Therapies
TL Lu, O Pugach, R Somerville, SA Rosenberg, JN Kochenderfer, M Better, SA Feldman
Human Gene Therapy Methods 2016
Fas/CD95 prevents autoimmunity independently of lipid raft localization and efficient apoptosis induction
AC Cruz, M Ramaswamy, C Ouyang, CA Klebanoff, P Sengupta, TN Yamamoto, F Meylan, SK Thomas, N Richoz, R Eil, S Price, R Casellas, VK Rao, J Lippincott-Schwartz, NP Restifo, RM Siegel
Nature Communications 2016
TNF superfamily cytokines in the promotion of Th9 differentiation and immunopathology
F Meylan, RM Siegel
Seminars in Immunopathology 2016

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