Reprogramming away from the exhausted T cell state

Karagiannis, Peter; Iriguchi, Shoichi; Kaneko, Shin

doi:10.1016/j.smim.2015.10.007

Cited by 25 publications

(20 citation statements)

References 180 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Polyfunctionality is a desirable feature of potent CD8 þ T cells, well known in infections (29), but only recently described in cancer immunity (11,30). This feature is known to correlate with antigen sensitivity and TCR affinity for cognate antigen (31,32), antigen concentration (33), and, partially, differentiation status (34). We recently showed that polyfunctional T cells dominate the periphery after successful TIL therapy for cancer (35).…”

Section: Polyfunctional Characterization Of Tumor-reactive Cd8 þ T Cellsmentioning

confidence: 99%

“…Polyfunctionality and proliferative potential can be dependent on the differentiation status of T cells (34). Because of quite high TNF production in unstimulated samples (TILs without tumor) and because CD8 þ CD107a þ T cells appeared less polyfunctional in RCC compared with metastatic melanoma (P ¼ 0.07; Supplementary Fig.…”

Section: Dysfunctional Profile Of Tumor-reactive Cd8 þ Tilsmentioning

confidence: 99%

See 1 more Smart Citation

T-cell Responses in the Microenvironment of Primary Renal Cell Carcinoma—Implications for Adoptive Cell Therapy

Andersen

Westergaard

Kjeldsen

et al. 2018

Cancer Immunology Research

View full text Add to dashboard Cite

expansion of large numbers of highly potent tumor-reactive T cells appears a prerequisite for effective adoptive cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TIL) as shown in metastatic melanoma (MM). We therefore sought to determine whether renal cell carcinomas (RCC) are infiltrated with tumor-reactive T cells that could be efficiently employed for adoptive transfer immunotherapy. TILs and autologous tumor cell lines (TCL) were successfully generated from 22 (92%) and 17 (77%) of 24 consecutive primary RCC specimens and compared with those generated from metastatic melanoma. Immune recognition of autologous TCLs or fresh tumor digests was observed in CD8 TILs from 82% of patients (18/22). Cytotoxicity assays confirmed the tumoricidal capacity of RCC-TILs. The overall expansion capacity of RCC-TILs was similar to MM-TILs. However, the magnitude, polyfunctionality, and ability to expand in classical expansion protocols of CD8 T-cell responses was lower compared with MM-TILs. The RCC-TILs that did react to the tumor were functional, and antigen presentation and processing of RCC tumors was similar to MM-TILs. Direct recognition of tumors with cytokine-induced overexpression of human leukocyte antigen class II was observed from CD4 T cells (6/12; 50%). Thus, TILs from primary RCC specimens could be isolated, expanded, and could recognize tumors. However, immune responses of expanded CD8 RCC-TILs were typically weaker than MM-TILs and displayed a mono-/oligofunctional pattern. The ability to select, enrich, and expand tumor-reactive polyfunctional T cells may be critical in developing effective ACT with TILs for RCC. In summary, TILs isolated from primary RCC specimens could recognize tumors. However, their immune responses were weaker than MM-TILs and displayed a mono-/oligofunctional pattern. The ability to select and expand polyfunctional T cells may improve cell therapy for RCC. .

show abstract

Section: Polyfunctional Characterization Of Tumor-reactive Cd8 þ T Cellsmentioning

confidence: 99%

Section: Dysfunctional Profile Of Tumor-reactive Cd8 þ Tilsmentioning

confidence: 99%

T-cell Responses in the Microenvironment of Primary Renal Cell Carcinoma—Implications for Adoptive Cell Therapy

Andersen

Westergaard

Kjeldsen

et al. 2018

Cancer Immunology Research

View full text Add to dashboard Cite

show abstract

“…In addition, isolation and banking of cord blood HSCs has been used to reconstitute the immune system for treatment of hematological disorders and may provide hope for homeostatic expansion of functional T cells [ 72 – 74 ]. (2) Reprogramming is a promising method to differentiate T cells away from exhausted and senescent states by redifferentiation from T-induced pluripotent stem cells (T-IPSCs) into naive and cytotoxic T cells or dedifferentiation within their own lineage [ 75 – 77 ]. Although generation of T cells from human embryonic stem cells (hESCs) and iPSCs was shown to be possible, the TCR repertoire due to seemingly random VDJ gene rearrangements remains unpredictable.…”

Section: Introductionmentioning

confidence: 99%

T cell senescence and CAR-T cell exhaustion in hematological malignancies

2018

View full text Add to dashboard Cite

T cell senescence has been recognized to play an immunosuppressive role in the aging population and cancer patients. Strategies dedicated to preventing or reversing replicative and premature T cell senescence are required to increase the lifespan of human beings and to reduce the morbidity from cancer. In addition, overcoming the T cell terminal differentiation or senescence from lymphoma and leukemia patients is a promising approach to enhance the effectiveness of adoptive cellular immunotherapy (ACT). Chimeric antigen receptor T (CAR-T) cell and T cell receptor-engineered T (TCR-T) cell therapy highly rely on functionally active T cells. However, the mechanisms which drive T cell senescence remain unclear and controversial. In this review, we describe recent progress for restoration of T cell homeostasis from age-related senescence as well as recovery of T cell activation in hematological malignancies.

show abstract

“… 7 , 51 , 52 , 53 To overcome the disadvantages faced in CAR-T and TCR-T cell production, an alternative approach has been attempted in the T cell regenerative field i.e., generating tumor-targeting T cells from human embryonic stem cell (hESC) or induced pluripotent stem cells (iPSCs). 52 , 54 , 55 In contrast to T cells generated from mouse ESCs, the induction of T cells from hESCs demonstrated limited success due to the failure of mimicking human thymus microenvironment in vivo. Generation of T cells from patient somatic cell-reprogrammed iPSCs demonstrated great potential in recent years.…”

Section: Redirected T Cellsmentioning

confidence: 99%

Approaches for generation of anti-leukemia specific T cells

Jin

2018

Cell Regeneration

View full text Add to dashboard Cite

As three decades ago, it was reported that adoptive T cell immunotherapy by infusion of autologous tumor infiltrating lymphocytes (TILs) mediated objective cancer regression in patients with metastatic melanoma. A new era of T cell immunotherapy arose since the improvement and clinical use of anti-CD19 chimeric antigen receptor T cells (CAR-T) for the treatment of refractory and relapsed B lymphocyte leukemia. However, several challenges and difficulties remain on the way to reach generic and effective T cell immunotherapy, including lacking a generic method for generating anti-leukemia-specific T cells from every patient. Here, we summarize the current methods of generating anti-leukemia-specific T cells, and the promising approaches in the future.

show abstract

Reprogramming away from the exhausted T cell state

Cited by 25 publications

References 180 publications

T-cell Responses in the Microenvironment of Primary Renal Cell Carcinoma—Implications for Adoptive Cell Therapy

T-cell Responses in the Microenvironment of Primary Renal Cell Carcinoma—Implications for Adoptive Cell Therapy

T cell senescence and CAR-T cell exhaustion in hematological malignancies

Approaches for generation of anti-leukemia specific T cells

Contact Info

Product

Resources

About