Stem-like CD8 T cells mediate response of adoptive cell immunotherapy against human cancer

Krishna, Sri; Lowery, Frank J.; Copeland, Amy R.; Bahadiroglu, Erol; Mukherjee, Ratnadeep; Li, Jia; Anibal, James; Sachs, Abraham; Adebola, Serifat; Gurusamy, Devikala; Yu, Zhiya; Hill, Victoria; Gartner, Jared J.; Li, Yong F.; Parkhurst, Maria R.; Paria, Biman C.; Kvistborg, Pia; Kelly, Michael C.; Goff, Stephanie L.; Altan‐Bonnet, Grégoire; Robbins, Paul F.; Rosenberg, Steven A.

doi:10.1126/science.abb9847

Cited by 298 publications

(246 citation statements)

References 66 publications

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“… 188 An increased understanding might facilitate in vitro strategies to increase the percentage of tumour-reactive stem-like TILs, for example, which have been shown to be capable of self-renewal, expansion, persistence and a superior anti-tumour response in patients with melanoma. 189 …”

Section: Cancer–immune System Interactionsmentioning

confidence: 99%

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Promises and challenges of adoptive T-cell therapies for solid tumours

et al. 2021

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Cancer is a leading cause of death worldwide and, despite new targeted therapies and immunotherapies, many patients with advanced-stage- or high-risk cancers still die, owing to metastatic disease. Adoptive T-cell therapy, involving the autologous or allogeneic transplant of tumour-infiltrating lymphocytes or genetically modified T cells expressing novel T-cell receptors or chimeric antigen receptors, has shown promise in the treatment of cancer patients, leading to durable responses and, in some cases, cure. Technological advances in genomics, computational biology, immunology and cell manufacturing have brought the aspiration of individualised therapies for cancer patients closer to reality. This new era of cell-based individualised therapeutics challenges the traditional standards of therapeutic interventions and provides opportunities for a paradigm shift in our approach to cancer therapy. Invited speakers at a 2020 symposium discussed three areas—cancer genomics, cancer immunology and cell-therapy manufacturing—that are essential to the effective translation of T-cell therapies in the treatment of solid malignancies. Key advances have been made in understanding genetic intratumour heterogeneity, and strategies to accurately identify neoantigens, overcome T-cell exhaustion and circumvent tumour immunosuppression after cell-therapy infusion are being developed. Advances are being made in cell-manufacturing approaches that have the potential to establish cell-therapies as credible therapeutic options. T-cell therapies face many challenges but hold great promise for improving clinical outcomes for patients with solid tumours.

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Section: Cancer–immune System Interactionsmentioning

confidence: 99%

“… 198 – 200 The enrichment of this subpopulation during TIL expansion could therefore enhance the efficacy of ACT therapies. 189 , 201 …”

Section: Cancer–immune System Interactionsmentioning

confidence: 99%

Promises and challenges of adoptive T-cell therapies for solid tumours

et al. 2021

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“…demonstrated that CD39 and CD69 expression can be used to bifurcate patient response to cell therapy and that some CD39 -TIL from these patients are neoantigen recognizing stem-like T cells, which are known to potentiate powerful antitumor responses 43 . Thus, it is likely that the reduced CD39 and overt expression of IL-2R and ICOS on T cells post CpG treatment potentiate T cell function, metabolism, and persistence in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, CD39 marks effector T cells that have an exhausted phenotype in patients with infectious disease and cancer and have reduced survival after activation in older individuals 28,29 42 . In patients with metastatic melanoma, Krishna et al demonstrated that CD39 and CD69 expression can be used to bifurcate patient response to cell therapy and that some CD39 - TIL from these patients are neoantigen recognizing stem-like T cells, which are known to potentiate powerful antitumor responses 43 . Thus, it is likely that the reduced CD39 and overt expression of IL-2Rα and ICOS on T cells post CpG treatment potentiate T cell function, metabolism, and persistence in vivo .…”

Section: Discussionmentioning

confidence: 99%

B cells imprint adoptively transferred CD8⁺T cells with enhanced tumor immunity

Smith

Knochelmann

Wyatt

et al. 2021

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Here we report a novel strategy to reverse the tolerant state of adoptively transferred CD8+ T cells against melanoma through ex vivo expansion with the TLR9 agonist CpG. T cells generated in the presence of CpG display potent anti-tumor efficacy without in vivo co-administration of high dose IL-2 or vaccination, which are classically required for effective treatment of solid tumors using adoptive cell therapies. CD8+ T cells adopt a unique proteomic signature and are characterized by an IL-2RhighαICOShighCD39low phenotype after CpG-mediated expansion. Surprisingly, we found that the presence of B cells, in the culture, was essential for imprinting CD8+ T cells with this phenotype and moreover purified B cells were sufficient to mediate the CpG-associated changes in T cells. These findings reveal a vital role for B cells in the generation of effective antitumor CD8+ T cells and have immediate implications for profoundly improving immunotherapy for patients.

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“…Metabolic fitness and T cell function are closely related and ways to target the T cell metabolism were recently reviewed. 103 For example, transient glucose restriction 104 and using stemlike CD8 cells 105 were shown to improve the efficacy of T cells in ACT approaches.…”

Section: Conclusion and Future Perspectivementioning

confidence: 99%

Advances in identification and selection of personalized neoantigen/T-cell pairs for autologous adoptive T cell therapies

et al. 2021

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Based on the success of tumor-infiltrating lymphocytes (TIL)-based therapies, personalized adoptive cell therapies (ACT) targeting neoantigens have the potential to become a disruptive technology and lead to highly effective treatments for cancer patients for whom no other options exist. ACT of TIL, peripheral blood or gene-engineered peripheral blood lymphocytes (PBLs) targeting neoantigens is a highly personalized intervention that requires three discrete steps: i) Identification of suitable personal targets (neoantigens), ii) selection of T cells or their T cell receptors (TCRs) that are specific for the identified neoantigens and iii) expansion of the selected T cell population or generation of sufficient number of TCR modified T cells. In this review, we provide an introduction into challenges and approaches to identify neoantigens and to select the Adoptive Cell Therapy, ACT, Neoantigen, T cell, Cancer respective neoantigen-reactive T cells for use in ACT.

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Stem-like CD8 T cells mediate response of adoptive cell immunotherapy against human cancer

Cited by 298 publications

References 66 publications

Promises and challenges of adoptive T-cell therapies for solid tumours

Promises and challenges of adoptive T-cell therapies for solid tumours

B cells imprint adoptively transferred CD8⁺T cells with enhanced tumor immunity

Advances in identification and selection of personalized neoantigen/T-cell pairs for autologous adoptive T cell therapies

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Stem-like CD8 T cells mediate response of adoptive cell immunotherapy against human cancer

Cited by 298 publications

References 66 publications

Promises and challenges of adoptive T-cell therapies for solid tumours

Promises and challenges of adoptive T-cell therapies for solid tumours

B cells imprint adoptively transferred CD8+T cells with enhanced tumor immunity

Advances in identification and selection of personalized neoantigen/T-cell pairs for autologous adoptive T cell therapies

Contact Info

Product

Resources

About

B cells imprint adoptively transferred CD8⁺T cells with enhanced tumor immunity