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Cited by 243

The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.

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

Open access
Klebanoff, Christopher A., Scott, Christopher D., Leonardi, Anthony J., Yamamoto, Tori N., Cruz, Anthony C., Ouyang, Claudia, Ramaswamy, Madhu, Roychoudhuri, Rahul, Ji, Yun, Eil, Robert L., Sukumar, Madhusudhanan, Crompton, Joseph G., Palmer, Douglas C., Borman, Zachary A., Clever, David, Thomas, Stacy K., Patel, Shashankkumar, Yu, Zhiya, Muranski, Pawel, Liu, Hui, Wang, Ena, Marincola, Francesco M., Gros, Alena, Gattinoni, Luca, Rosenberg, Steven A., Siegel, Richard M., Restifo, Nicholas P.·2015·Journal of Clinical Investigation
DOI 10.1172/jci81217
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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.

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Metadata

Authors
Klebanoff, C. A., Scott, C. D., Leonardi, A. J., Yamamoto, T. N., Cruz, A. C., Ouyang, C., Ramaswamy, M., Roychoudhuri, R., Ji, Y., Eil, R. L., Sukumar, M., Crompton, J. G., Palmer, D. C., Borman, Z. A., Clever, D., Thomas, S. K., Patel, S., Yu, Z., Muranski, P., Liu, H., Wang, E., Marincola, F. M., Gros, A., Gattinoni, L., Rosenberg, S. A., Siegel, R. M., & Restifo, N. P.
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
2015-12-14
Volume
126
Issue
1
Pages
318-334
ISSN
  • 0021-9738 (ISSN-L)
  • 1558-8238
DOI
10.1172/jci81217
OpenAlex
W2211359813
Cited by
243
References
12
FWCI
9.48
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Memory T cell–driven differentiation of naive cells impairs adoptive immunotherapy. https://app.cochat.ai/papers/10.1172/jci81217
The paper
Klebanoff, C. A., Scott, C. D., Leonardi, A. J., Yamamoto, T. N., Cruz, A. C., Ouyang, C., Ramaswamy, M., Roychoudhuri, R., Ji, Y., Eil, R. L., Sukumar, M., Crompton, J. G., Palmer, D. C., Borman, Z. A., Clever, D., Thomas, S. K., Patel, S., Yu, Z., Muranski, P., . . . Restifo, N. P. (2015). Memory T cell–driven differentiation of naive cells impairs adoptive immunotherapy. Journal of Clinical Investigation. https://doi.org/10.1172/jci81217

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.