T-bet and Eomesodermin Are Required for T Cell-Mediated Antitumor Immune Responses

Zhu, Yueyong; Ju, Songguang; Chen, Elizabeth; Dai, Shao; Li, Changyou; Morel, Penelope A.; Liu, Lin; Zhang, Xueguang; Lu, Binfeng

doi:10.4049/jimmunol.1000749

Cited by 161 publications

(166 citation statements)

References 34 publications

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“…51 In addition, they coordinately promote T cell migration to inflamed tissues via chemokine receptors and cooperate to generate cytotoxic T cells. [52][53][54] In mice, CTLA-4 reduces the expression of eomes at the transcriptional level resulting in less IFNg and granzyme B producing CD8 C T cells. 55 In accordance with this observation, our results showed that CTLA-4 blockade induced a higher expression of eomes in CD8 C T cells from patients with DC, suggesting a pivotal role of this transcriptional factor during ipilimumab therapy.…”

Section: Discussionmentioning

confidence: 99%

Ipilimumab reshapes T cell memory subsets in melanoma patients with clinical response

et al. 2016

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Purpose: Therapy targeting CTLA-4 immune checkpoint provides increased survival in patients with advanced melanoma. However, immunotherapy is frequently associated with delayed and heterogeneous clinical responses and it is important to identify prognostic immunological correlates of clinical endpoints. Experimental design: 77 patients with stage III/IV melanoma were treated with ipilimumab alone every 3 weeks, during 9 weeks. Blood samples were collected at the baseline and before each dose for in depth immune monitoring. Results: The median follow-up was 28 mo with a median survival of 7 mo. Survival and clinical benefit were significantly improved when absolute lymphocyte count at the baseline was above 1 £ 10 9 /L. Notably, ipilimumab had a global effect on memory T cells, with an early increase of central and effector subsets in patients with disease control. By contrast, percentages of stem cell memory T cells (TSCM) gradually decreased despite stable absolute counts and sustained proliferation, suggesting a process of differentiation. Higher proportions of eomes C and Ki-67 C T cells were observed, with enhanced skin homing potential and induction of cytotoxic markers. Conclusion: These results suggest that CTLA-4 blockade is able to reshape the memory subset with the potential involvement of Eomes and memory subsets including TSCM.

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Section: Discussionmentioning

confidence: 99%

Ipilimumab reshapes T cell memory subsets in melanoma patients with clinical response

et al. 2016

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“…[25][26][27] Recent studies have indicated that the administration of long peptides encompassing Th1 and CTL epitopes has the potential to elicit both CD4…”

Section: Discussionmentioning

confidence: 99%

“…23,24 In addition, both T-box transcription factors cooperate to promote cytotoxic T lymphocyte (CTL) formation by inducing the expression of perforin and granzyme B during early stages of CD8 C T cell activation and promote migration to inflamed tissues by inducing chemokine receptors. [25][26][27] Importantly, sufficient clinical evidence demonstrates a correlation between longer survival of cancer patients and increased expression of genes representing type 1 effector T cells, in particular T-bet and Eomes. [28][29][30] Therefore, T-bet and Eomes are critical for both function and homeostasis of effector and memory T cells.…”

Section: Introductionmentioning

confidence: 99%

Heteroclitic XBP1 peptides evoke tumor-specific memory cytotoxic T lymphocytes against breast cancer, colon cancer, and pancreatic cancer cells

et al. 2014

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Keywords: breast / colon / pancreatic cancer, cancer vaccine, heteroclitic peptides, XBP1XBP1 is a critical transcriptional activator of the unfolded protein response (UPR), which increases tumor cell survival under prolonged endoplasmic reticulum (ER) stress and hypoxic conditions.This study was designed to evaluate the immunogenicity of heteroclitic XBP1 unspliced (US) [184][185][186][187][188][189][190][191][192] (YISPWILAV) and heteroclictic XBP1 spliced (SP) [367][368][369][370][371][372][373][374][375] (YLFPQLISV) HLA-A2 peptides, and to characterize the specific activities of XBP1 peptides-specific cytotoxic T lymphocytes (XBP1-CTL) against breast cancer, colon cancer, and pancreatic cancer cells.The XBP1-CTL had upregulated expression of critical T cell markers and displayed HLA-A2-restricted and antigen-specific activities against breast cancer, colon cancer and pancreatic cancer cells. XBP1-CTL were enriched withCD45RO C memory CTL, which showed high expression of critical T cell markers (CD28, ICOS, CD69, CD40L), cell proliferation and antitumor activities as compared to CD45RO ¡ non-memory CTL. The effector memory (EM: CD45RO C CCR7 ¡ ) subset had the highest level of cell proliferation while the central memory (CM: CD45ROC CCR7 C ) subset demonstrated enhanced functional activities (CD107a degranulation, IFNg/IL-2 production) upon recognition of the respective tumor cells. Furthermore, both the EM and CM XBP1-CTL subsets expressed high levels of Th1 transcription regulators Tbet and Eomes. The highest frequencies of IFNg or granzyme B producing cells were detected within CM XBP1-CTL subset that were either Tbet C or Eomes C in responding to the tumor cells.These results demonstrate the immunotherapeutic potential of a cocktail of immunogenic HLA-A2 specific heteroclitic XBP1 US [184][185][186][187][188][189][190][191][192] and heteroclictic XBP1 SP 367-375 peptides to induce CD3 C CD8C CTL enriched for CM and EM cells with specific antitumor activities against a variety of solid tumors.

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“…Two subsets of CD8 + T cells are now known to enhance cytotoxic responses, namely IFN-γ-producing CD8 + T cells (Tc1) and IL-17-producing CD8 + T cells (Tc17). 10,11,42,43 Zou showed that a chemical adjuvant, praziquantel (PZQ), could be used to elicit Tc17 cells in HBV DNA vaccination and contributed to viral antigen clearance in a HBsAg-transgenic mouse model. 11 Tc1 is a classical cytotoxic CD8 + T cell, producing IFN-γ and TNF-α and cytolytic effects by secreting perforin and granzyme B when in contact with target cells.…”

Section: Cloning Of Murine Il-22 and Expression In Bhk Cellsmentioning

confidence: 99%

Interleukin-22 as a molecular adjuvant facilitates IL-17-producing CD8⁺T cell responses against a HBV DNA vaccine in mice

Zou

et al. 2013

Human Vaccines & Immunotherapeutics

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T-bet and Eomesodermin Are Required for T Cell-Mediated Antitumor Immune Responses

Abstract: Material Supplementary 9.DC1http://www.jimmunol.org/content/suppl/2010/08/16/jimmunol.100074

Cited by 161 publications

References 34 publications

Ipilimumab reshapes T cell memory subsets in melanoma patients with clinical response

Ipilimumab reshapes T cell memory subsets in melanoma patients with clinical response

Heteroclitic XBP1 peptides evoke tumor-specific memory cytotoxic T lymphocytes against breast cancer, colon cancer, and pancreatic cancer cells

Interleukin-22 as a molecular adjuvant facilitates IL-17-producing CD8⁺T cell responses against a HBV DNA vaccine in mice

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T-bet and Eomesodermin Are Required for T Cell-Mediated Antitumor Immune Responses

Abstract: Material Supplementary 9.DC1http://www.jimmunol.org/content/suppl/2010/08/16/jimmunol.100074

Cited by 161 publications

References 34 publications

Ipilimumab reshapes T cell memory subsets in melanoma patients with clinical response

Ipilimumab reshapes T cell memory subsets in melanoma patients with clinical response

Heteroclitic XBP1 peptides evoke tumor-specific memory cytotoxic T lymphocytes against breast cancer, colon cancer, and pancreatic cancer cells

Interleukin-22 as a molecular adjuvant facilitates IL-17-producing CD8+T cell responses against a HBV DNA vaccine in mice

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Product

Resources

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Interleukin-22 as a molecular adjuvant facilitates IL-17-producing CD8⁺T cell responses against a HBV DNA vaccine in mice