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Increased proportion of exhausted T cells

MedGen UID:
1620482
•Concept ID:
C4531071
•
Finding
HPO: HP:0031514

Definition

An abnormally elevated proportion of exhausted T cells (Tex) among circulating T cells. T cell exhaustion is a distinct differentiation state that can be distinguished from naive, effector, and memory T cells. Compared to effector (TE) and memory (TMEM) T cells, exhausted T cells (TEX) display impaired effector functions (e.g., rapid production of effector cytokines, cytotoxicity). TEX have limited proliferative potential, especially compared to some subsets of TMEM and naive T cells. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVIncreased proportion of exhausted T cells

Conditions with this feature

Epidermodysplasia verruciformis, susceptibility to, 4
MedGen UID:
1648396
•Concept ID:
C4749042
•
Finding
Epidermodysplasia verruciformis-4 is an autosomal recessive immunologic disorder characterized by increased susceptibility to certain human papilloma viruses (HPV) that cause warts and skin lesions. Affected individuals present in childhood with disseminated flat warts and psoriatic-like lesions that do not respond to treatment. Immunologic workup shows defects in T-cell development and signaling (summary by Crequer et al., 2012). For a discussion of genetic heterogeneity of susceptibility to epidermodysplasia verruciformis, see EV1 (226400).
See: Condition Record
Epidermodysplasia verruciformis, susceptibility to, 4

Professional guidelines

PubMed

Treatment with oncolytic vaccinia virus infects tumor-infiltrating regulatory and exhausted T cells.
DePeaux K, Gunn WG, Rivadeneira DB, Delgoffe GM
J Immunother Cancer 2024 Aug 17;12(8) doi: 10.1136/jitc-2024-009062. PMID: 39153823Free PMC Article
T-cell response to checkpoint blockade immunotherapies: from fundamental mechanisms to treatment signatures.
Elliot TAE, Lecky DAJ, Bending D
Essays Biochem 2023 Sep 28;67(6):967-977. doi: 10.1042/EBC20220247. PMID: 37386922Free PMC Article
Definition of B cell helper T cells in rheumatoid arthritis and their behavior during treatment.
Lucas C, Perdriger A, Amé P
Semin Arthritis Rheum 2020 Oct;50(5):867-872. Epub 2020 Jul 13 doi: 10.1016/j.semarthrit.2020.06.021. PMID: 32896702

Recent clinical studies

Etiology

Myeloid-derived suppressor cells-induced exhaustion of CD8 + T-cell participates in rejection after liver transplantation.
Zhou LX, Jiang YZ, Li XQ, Zhang JM, Li SP, Wei L, Zhang HM, Zhou GP, Chen XJ, Sun LY, Zhu ZJ
Cell Death Dis 2024 Jul 16;15(7):507. doi: 10.1038/s41419-024-06834-z. PMID: 39013845Free PMC Article
Cholesterol induction in CD8(+) T cell exhaustion in colorectal cancer via the regulation of endoplasmic reticulum-mitochondria contact sites.
Shuwen H, Yinhang W, Jing Z, Qiang Y, Yizhen J, Quan Q, Yin J, Jiang L, Xi Y
Cancer Immunol Immunother 2023 Dec;72(12):4441-4456. Epub 2023 Nov 3 doi: 10.1007/s00262-023-03555-8. PMID: 37919522Free PMC Article
Cordycepin synergizes with CTLA-4 blockade to remodel the tumor microenvironment for enhanced cancer immunotherapy.
Chen L, Zheng X, Huang H, Feng C, Wu S, Chen R, Jiang H, Yuan M, Fu Y, Ying H, Zhou J, Jiang J
Int Immunopharmacol 2023 Nov;124(Pt A):110786. Epub 2023 Aug 21 doi: 10.1016/j.intimp.2023.110786. PMID: 37611443
Accelerated Maturation, Exhaustion, and Senescence of T cells in 22q11.2 Deletion Syndrome.
Smetanova J, Milota T, Rataj M, Bloomfield M, Sediva A, Klocperk A
J Clin Immunol 2022 Feb;42(2):274-285. Epub 2021 Oct 29 doi: 10.1007/s10875-021-01154-9. PMID: 34716533
Evaluation of Exhausted Regulatory T Cells in Preeclampsia.
Daraei N, Ghafourian M, Ghadiri A, Amari A, Najafian M, Rokhafrooz S
Iran J Immunol 2019 Jun;16(2):163-169. doi: 10.22034/IJI.2019.80259. PMID: 31182690

Diagnosis

T-Cell Characteristics Impact Response and Resistance to T-Cell-Redirecting Bispecific Antibodies in Multiple Myeloma.
Verkleij CPM, O'Neill CA, Broekmans MEC, Frerichs KA, Bruins WSC, Duetz C, Kruyswijk S, Baglio SR, Skerget S, Montes de Oca R, Zweegman S, Verona RI, Mutis T, van de Donk NWCJ
Clin Cancer Res 2024 Jul 15;30(14):3006-3022. doi: 10.1158/1078-0432.CCR-23-3333. PMID: 38687588
Single-Cell Transcriptome Reveals Potential Mechanisms for Coronary Artery Lesions in Kawasaki Disease.
Chen Y, Yang M, Zhang M, Wang H, Zheng Y, Sun R, Li X
Arterioscler Thromb Vasc Biol 2024 Apr;44(4):866-882. Epub 2024 Feb 15 doi: 10.1161/ATVBAHA.123.320188. PMID: 38357816
Single-cell mapping reveals several immune subsets associated with liver metastasis of pancreatic ductal adenocarcinoma.
Zhang Z, Zhu XQ, Yang F, Lai NN, Zhu L, Cole K, Hu BY, Li TE, Zhu Y, Zhang LM, Wang S, Zheng Y, Mao H, Zhao Y, Bruns C, Vago R, Tu B, Wong JWH, Fu DL, Qin LX, Dong QZ
Med 2023 Oct 13;4(10):728-743.e7. Epub 2023 Aug 25 doi: 10.1016/j.medj.2023.07.010. PMID: 37633269
Increased Level of Tim-3(+)PD-1(+)CD4(+)T Cells With Altered Function Might Be Associated With Lower Extremity Arteriosclerosis Obliterans.
Cui L, Chen L, Dai Y, Ou J, Qiu M, Wang S
Front Immunol 2022;13:871362. Epub 2022 Jun 10 doi: 10.3389/fimmu.2022.871362. PMID: 35757718Free PMC Article
Differences between exhausted CD8(+) T cells in hepatocellular carcinoma patients with and without uremia.
Xiaohong C, Jianzhou Z, Bo S, Wenlv L, Xuesen C, Fangfang X
Can J Physiol Pharmacol 2021 Apr;99(4):395-401. Epub 2020 Aug 15 doi: 10.1139/cjpp-2019-0641. PMID: 32799654

Therapy

Macro CD5L(+) deteriorates CD8(+)T cells exhaustion and impairs combination of Gemcitabine-Oxaliplatin-Lenvatinib-anti-PD1 therapy in intrahepatic cholangiocarcinoma.
Lu JC, Wu LL, Sun YN, Huang XY, Gao C, Guo XJ, Zeng HY, Qu XD, Chen Y, Wu D, Pei YZ, Meng XL, Zheng YM, Liang C, Zhang PF, Cai JB, Ding ZB, Yang GH, Ren N, Huang C, Wang XY, Gao Q, Sun QM, Shi YH, Qiu SJ, Ke AW, Shi GM, Zhou J, Sun YD, Fan J
Nat Commun 2024 Jan 20;15(1):621. doi: 10.1038/s41467-024-44795-1. PMID: 38245530Free PMC Article
Landscape of Immune Cells Heterogeneity in Liver Transplantation by Single-Cell RNA Sequencing Analysis.
Li X, Li S, Wu B, Xu Q, Teng D, Yang T, Sun Y, Zhao Y, Li T, Liu D, Yang S, Gong W, Cai J
Front Immunol 2022;13:890019. Epub 2022 May 10 doi: 10.3389/fimmu.2022.890019. PMID: 35619708Free PMC Article
Neoadjuvant PD-1 blockade induces T cell and cDC1 activation but fails to overcome the immunosuppressive tumor associated macrophages in recurrent glioblastoma.
Lee AH, Sun L, Mochizuki AY, Reynoso JG, Orpilla J, Chow F, Kienzler JC, Everson RG, Nathanson DA, Bensinger SJ, Liau LM, Cloughesy T, Hugo W, Prins RM
Nat Commun 2021 Nov 26;12(1):6938. doi: 10.1038/s41467-021-26940-2. PMID: 34836966Free PMC Article
Combination of PD-1 Inhibitor and OX40 Agonist Induces Tumor Rejection and Immune Memory in Mouse Models of Pancreatic Cancer.
Ma Y, Li J, Wang H, Chiu Y, Kingsley CV, Fry D, Delaney SN, Wei SC, Zhang J, Maitra A, Yee C
Gastroenterology 2020 Jul;159(1):306-319.e12. Epub 2020 Mar 14 doi: 10.1053/j.gastro.2020.03.018. PMID: 32179091Free PMC Article
LAG3 (CD223) as a cancer immunotherapy target.
Andrews LP, Marciscano AE, Drake CG, Vignali DA
Immunol Rev 2017 Mar;276(1):80-96. doi: 10.1111/imr.12519. PMID: 28258692Free PMC Article

Prognosis

Exhausted Tumor-infiltrating CD39+CD103+ CD8+ T Cells Unveil Potential for Increased Survival in Human Pancreatic Cancer.
Gorchs L, Fernández-Moro C, Asplund E, Oosthoek M, Solders M, Ghorbani P, Sparrelid E, Rangelova E, Löhr MJ, Kaipe H
Cancer Res Commun 2024 Feb 19;4(2):460-474. doi: 10.1158/2767-9764.CRC-23-0405. PMID: 38335302Free PMC Article
Macro CD5L(+) deteriorates CD8(+)T cells exhaustion and impairs combination of Gemcitabine-Oxaliplatin-Lenvatinib-anti-PD1 therapy in intrahepatic cholangiocarcinoma.
Lu JC, Wu LL, Sun YN, Huang XY, Gao C, Guo XJ, Zeng HY, Qu XD, Chen Y, Wu D, Pei YZ, Meng XL, Zheng YM, Liang C, Zhang PF, Cai JB, Ding ZB, Yang GH, Ren N, Huang C, Wang XY, Gao Q, Sun QM, Shi YH, Qiu SJ, Ke AW, Shi GM, Zhou J, Sun YD, Fan J
Nat Commun 2024 Jan 20;15(1):621. doi: 10.1038/s41467-024-44795-1. PMID: 38245530Free PMC Article
Single-cell atlas reveals a distinct immune profile fostered by T cell-B cell crosstalk in triple negative breast cancer.
Ding S, Qiao N, Zhu Q, Tong Y, Wang S, Chen X, Tian Q, Xiao Y, Shen K
Cancer Commun (Lond) 2023 Jun;43(6):661-684. Epub 2023 May 9 doi: 10.1002/cac2.12429. PMID: 37158690Free PMC Article
Fibrinogen-like protein 1 promotes liver-resident memory T-cell exhaustion in hepatocellular carcinoma.
Yang C, Qian Q, Zhao Y, Huang B, Chen R, Gong Q, Ji H, Wang C, Xia L, You Z, Zhang J, Chen X
Front Immunol 2023;14:1112672. Epub 2023 Mar 13 doi: 10.3389/fimmu.2023.1112672. PMID: 36993960Free PMC Article
Resolving the difference between left-sided and right-sided colorectal cancer by single-cell sequencing.
Guo W, Zhang C, Wang X, Dou D, Chen D, Li J
JCI Insight 2022 Jan 11;7(1) doi: 10.1172/jci.insight.152616. PMID: 34793335Free PMC Article

Clinical prediction guides

Macro CD5L(+) deteriorates CD8(+)T cells exhaustion and impairs combination of Gemcitabine-Oxaliplatin-Lenvatinib-anti-PD1 therapy in intrahepatic cholangiocarcinoma.
Lu JC, Wu LL, Sun YN, Huang XY, Gao C, Guo XJ, Zeng HY, Qu XD, Chen Y, Wu D, Pei YZ, Meng XL, Zheng YM, Liang C, Zhang PF, Cai JB, Ding ZB, Yang GH, Ren N, Huang C, Wang XY, Gao Q, Sun QM, Shi YH, Qiu SJ, Ke AW, Shi GM, Zhou J, Sun YD, Fan J
Nat Commun 2024 Jan 20;15(1):621. doi: 10.1038/s41467-024-44795-1. PMID: 38245530Free PMC Article
Cholesterol induction in CD8(+) T cell exhaustion in colorectal cancer via the regulation of endoplasmic reticulum-mitochondria contact sites.
Shuwen H, Yinhang W, Jing Z, Qiang Y, Yizhen J, Quan Q, Yin J, Jiang L, Xi Y
Cancer Immunol Immunother 2023 Dec;72(12):4441-4456. Epub 2023 Nov 3 doi: 10.1007/s00262-023-03555-8. PMID: 37919522Free PMC Article
Single-cell atlas reveals a distinct immune profile fostered by T cell-B cell crosstalk in triple negative breast cancer.
Ding S, Qiao N, Zhu Q, Tong Y, Wang S, Chen X, Tian Q, Xiao Y, Shen K
Cancer Commun (Lond) 2023 Jun;43(6):661-684. Epub 2023 May 9 doi: 10.1002/cac2.12429. PMID: 37158690Free PMC Article
Neoadjuvant PD-1 blockade induces T cell and cDC1 activation but fails to overcome the immunosuppressive tumor associated macrophages in recurrent glioblastoma.
Lee AH, Sun L, Mochizuki AY, Reynoso JG, Orpilla J, Chow F, Kienzler JC, Everson RG, Nathanson DA, Bensinger SJ, Liau LM, Cloughesy T, Hugo W, Prins RM
Nat Commun 2021 Nov 26;12(1):6938. doi: 10.1038/s41467-021-26940-2. PMID: 34836966Free PMC Article
LAG3 (CD223) as a cancer immunotherapy target.
Andrews LP, Marciscano AE, Drake CG, Vignali DA
Immunol Rev 2017 Mar;276(1):80-96. doi: 10.1111/imr.12519. PMID: 28258692Free PMC Article

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