scholarly journals TNF-α Induction of GM2 Expression on Renal Cell Carcinomas Promotes T Cell Dysfunction

2007 ◽  
Vol 178 (10) ◽  
pp. 6642-6652 ◽  
Author(s):  
Gira Raval ◽  
Soumika Biswas ◽  
Patricia Rayman ◽  
Kaushik Biswas ◽  
Gaurisankar Sa ◽  
...  
Keyword(s):  
T Cell ◽  
Renal Cell ◽  
Renal Cell Carcinomas ◽  
Cell Dysfunction ◽  
Tnf Α ◽  
T Cell Dysfunction

scholarly journals Mixed signature of activation and dysfunction allows human decidual CD8+ T cells to provide both tolerance and immunity

2017 ◽  
Vol 115 (2) ◽  
pp. 385-390 ◽  
Author(s):  
Anita van der Zwan ◽  
Kevin Bi ◽  
Errol R. Norwitz ◽  
Ângela C. Crespo ◽  
Frans H. J. Claas ◽  
...  
Keyword(s):  
T Cell ◽  
Gene Expression Analysis ◽  
Effector Memory ◽  
Transcriptional Signature ◽  
Cell Dysfunction ◽  
Tnf Α ◽  
T Cell Dysfunction ◽  
Ifn Γ ◽  
Fetal Antigens

Understanding how decidual CD8+ T cell (CD8+ dT) cytotoxicity is regulated and how these cells integrate the competing needs for maternal–fetal tolerance and immunity to infection is an important research and clinical goal. Gene-expression analysis of effector-memory CD8+ dT demonstrated a mixed transcriptional signature of T cell dysfunction, activation, and effector function. High protein expression of coinhibitory molecules PD1, CTLA4, and LAG3, accompanied by low expression of cytolytic molecules suggests that the decidual microenvironment reduces CD8+ dT effector responses to maintain tolerance to fetal antigens. However, CD8+ dT degranulated, proliferated, and produced IFN-γ, TNF-α, perforin, and granzymes upon in vitro stimulation, demonstrating that CD8+ dT are not permanently suppressed and retain the capacity to respond to proinflammatory events, such as infections. The balance between transient dysfunction of CD8+ dT that are permissive of placental and fetal development, and reversal of this dysfunctional state, is crucial in understanding the etiology of pregnancy complications and prevention of congenital infections.

scholarly journals Elevated Levels of Select Gangliosides in T Cells from Renal Cell Carcinoma Patients Is Associated with T Cell Dysfunction

2009 ◽  
Vol 183 (8) ◽  
pp. 5050-5058 ◽  
Author(s):  
Soumika Biswas ◽  
Kaushik Biswas ◽  
Amy Richmond ◽  
Jennifer Ko ◽  
Sankar Ghosh ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cells ◽  
T Cell ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cell Dysfunction ◽  
T Cell Dysfunction

GM2 Expression in Renal Cell Carcinoma: Potential Role in Tumor-Induced T-Cell Dysfunction

2006 ◽  
Vol 66 (13) ◽  
pp. 6816-6825 ◽  
Author(s):  
Kaushik Biswas ◽  
Amy Richmond ◽  
Patricia Rayman ◽  
Soumika Biswas ◽  
Mark Thornton ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cell ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Potential Role ◽  
Cell Dysfunction ◽  
T Cell Dysfunction

scholarly journals A mosaic renal myeloid subtype with T-cell inhibitory and protumoral features is linked to immune escape and survival in clear cell renal cell cancer

2020 ◽  
Author(s):  
Dorothee Brech ◽  
Tobias Straub ◽  
Evangelos Kokolakis ◽  
Martin Irmler ◽  
Johannes Beckers ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cells ◽  
T Cell ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Patient Survival ◽  
Mononuclear Phagocytes ◽  
Cell Dysfunction ◽  
T Cell Dysfunction ◽  
Cell Inhibition

SummaryMononuclear phagocytes moderate tissue repair, immune activation and tolerance. In the renal tubulo-interstitium specialized dendritic cells help maintain homeostasis and protect tubuli from immune injury. Human renal cell carcinoma (RCC) is immunogenic; yet immunotherapies that target T-cell dysfunction show limited clinical efficacy suggesting additional mechanisms of immunoinhibiton. We previously described “enriched-in-renal cell carcinoma” (erc)DCs that are often found in tight contact with T cells which are dysfunctional. Here we describe that ercDCs exhibit a distinct polarization state imparted by tissue-specific signals characteristic for RCC and renal tissue homeostasis. The resulting mosaic transcript signature includes features associated with host defense activity, angiogenesis/invasion and T-cell inhibition. An ercDC-specific profile was predictive for patient survival and suggests potential therapeutic targets for improved immunotherapy.SignificanceImmunotherapies, which re-invigorate T-cell activity, achieve clinical responses in subsets of patients only revealing additional layers of T-cell inhibition. Mononuclear phagocytes can be immunoinhibitory. But, they are highly plastic and repolarization may be possible if key programming molecules can be identified, potentially enabling antitumor responses in tumors refractory to checkpoint blockade. We describe a myeloid cell type with mosaic feature including tumor-promotion and immunoinhibition in human clear cell renal cell carcinoma. Observed tight contacts with T cells may translate into T-cell dysfunction. A high ercDC score in tumor tissue correlates with poor patient survival suggesting ercDCs as targets for therapeutic intervention. Targeting molecules that are identified in the ercDC profile may expand the range of patients effectively treated by immunotherapy.HighlightsBullet points:Renal cell carcinoma (ccRCC) harbors polarized mosaic myeloid cells (ercDCs)ercDCs are found in contact with dysfunctional T cells in ccRCCercDCs express novel immunoinhibitory proteinsHigh ercDC z-score in ccRCC tissue correlates with poor patient survival

The resistance of HIV‐infected chimpanzees to progression to AIDS correlates with absence of HIV‐related T‐cell dysfunction

1993 ◽  
Vol 22 (2-3) ◽  
pp. 194-200 ◽  
Author(s):  
Jonathan Heeney ◽  
Richard Jonker ◽  
Wim Koornstra ◽  
Rob Dubbes ◽  
Henk Niphuis ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Dysfunction ◽  
T Cell Dysfunction

scholarly journals Tim-3 adaptor protein Bat3 is a molecular checkpoint of T cell terminal differentiation and exhaustion

2021 ◽  
Vol 7 (18) ◽  
pp. eabd2710
Author(s):  
Chen Zhu ◽  
Karen O. Dixon ◽  
Kathleen Newcomer ◽  
Guangxiang Gu ◽  
Sheng Xiao ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Adaptor Protein ◽  
Transcriptional Analysis ◽  
T Cell Exhaustion ◽  
Cell Exhaustion ◽  
Cell Dysfunction ◽  
Autoreactive T Cell ◽  
Autoimmune Conditions ◽  
T Cell Dysfunction

T cell exhaustion has been associated with poor prognosis in persistent viral infection and cancer. Conversely, in the context of autoimmunity, T cell exhaustion has been favorably correlated with long-term clinical outcome. Understanding the development of exhaustion in autoimmune settings may provide underlying principles that can be exploited to quell autoreactive T cells. Here, we demonstrate that the adaptor molecule Bat3 acts as a molecular checkpoint of T cell exhaustion, with deficiency of Bat3 promoting a profound exhaustion phenotype, suppressing autoreactive T cell–mediated neuroinflammation. Mechanistically, Bat3 acts as a critical mTORC2 inhibitor to suppress Akt function. As a result, Bat3 deficiency leads to increased Akt activity and FoxO1 phosphorylation, indirectly promoting Prdm1 expression. Transcriptional analysis of Bat3−/− T cells revealed up-regulation of dysfunction-associated genes, concomitant with down-regulation of genes associated with T cell effector function, suggesting that absence of Bat3 can trigger T cell dysfunction even under highly proinflammatory autoimmune conditions.

scholarly journals 52350 PKM2 mediates anti-tumor immunity and T cell dysfunction

2021 ◽  
pp. 1-2
Author(s):  
Geoffrey Markowitz ◽  
Yi Ban ◽  
Michael Crowley ◽  
Diamile Tavarez ◽  
Stephen T.C. Wong ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Immunity ◽  
Cell Dysfunction ◽  
T Cell Dysfunction

scholarly journals Co-delivery of IOX1 and doxorubicin for antibody-independent cancer chemo-immunotherapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Liu ◽  
Zhihao Zhao ◽  
Nasha Qiu ◽  
Quan Zhou ◽  
Guowei Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Programmed Cell Death ◽  
Memory Function ◽  
Histone Demethylase ◽  
Cell Dysfunction ◽  
T Cell Infiltration ◽  
Programmed Cell Death 1 ◽  
T Cell Dysfunction

AbstractAnti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) antibodies are currently used in the clinic to interupt the PD-1/PD-L1 immune checkpoint, which reverses T cell dysfunction/exhaustion and shows success in treating cancer. Here, we report a histone demethylase inhibitor, 5-carboxy-8-hydroxyquinoline (IOX1), which inhibits tumour histone demethylase Jumonji domain-containing 1A (JMJD1A) and thus downregulates its downstream β-catenin and subsequent PD-L1, providing an antibody-independent paradigm interrupting the PD-1/PD-L1 checkpoint. Synergistically, IOX1 inhibits cancer cells’ P-glycoproteins (P-gp) through the JMJD1A/β-catenin/P-gp pathway and greatly enhances doxorubicin (DOX)-induced immune-stimulatory immunogenic cell death. As a result, the IOX1 and DOX combination greatly promotes T cell infiltration and activity and significantly reduces tumour immunosuppressive factors. Their liposomal combination reduces the growth of various murine tumours, including subcutaneous, orthotopic, and lung metastasis tumours, and offers a long-term immunological memory function against tumour rechallenging. This work provides a small molecule-based potent cancer chemo-immunotherapy.

scholarly journals Sweet T Cell Dysfunction

2018 ◽  
Vol 18 (4) ◽  
pp. 775-775
Author(s):  
Maria-Luisa Alegre
Keyword(s):  
T Cell ◽  
Cell Dysfunction ◽  
T Cell Dysfunction
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