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Risk Factors for Dementia among Race and Ethnic Populations in the United States
Published in Gwen Yeo, Linda A. Gerdner, Dolores Gallagher-Thompson, Ethnicity and the Dementias, 2018
Several other candidate genes may play an important role in risk for African Americans, specifically. In genome wide meta-analyses of genetic risk factors for late onset AD among 5,896 African Americans from 12 datasets, 42 researches from the AD Genetics Consortium found that the strongest association was with the APOE gene, but there was also a strong association with ABCA7, a protein transporter gene previously found to have a weaker association with AD in European White populations (Reitz et al., 2013). The following other genetic factors were reported to be related to AD among African Americans in individual studies: SORL1 (Lee et al., 2007), TP73 (Li et al., 2004) and PVRL2 (Logue et al., 2011). A preliminary report suggests that CETP V405 valine homozygosity is associated with slower memory decline and lower risk for incident AD among African Americans (Sanders et al., 2010). However, a genetic risk score for AD based on the 10 most commonly found genetic loci was found to predict AD more weakly in non-Hispanic Blacks than among non-Hispanic Whites (Marden, Walter, Tchetgen Tchetgen, Kawachi, & Glymour, 2014).
Upregulation of TIGIT and PD-1 in Colorectal Cancer with Mismatch-repair Deficiency
Published in Immunological Investigations, 2021
Xuebing Zhou, Xiaoling Ding, Hai Li, Chun Yang, Zhanbing Ma, Guangxian Xu, Shaoqi Yang, Dong Zhang, Xiaoliang Xie, Lei Xin, Xiaoli Luo
T cell Ig and ITIM domain (TIGIT) is an inhibitory receptor that is expressed by activated T cells, Tregs, and NK cells (Chauvin et al. 2015). The ligands of TIGIT are the adhesion molecules CD155 (Necl-5, also known as PVR; high affinity) and CD112 (nectin-2, also known as PRR2 or PVRL2; low affinity) (Stanietsky et al. 2009; Stengel et al. 2012; Yu et al. 2009). TIGIT is upregulated and plays an inhibitory role in a broad range of solid tumors and chronic viral infections (Manieri et al. 2017). As a coinhibitory receptor, TIGIT activation promotes the suppressive function of the Tregs. TIGIT expression is higher on FOXP3+ Tregs than on FOXP3- CD4+ TILs in the B16 melanoma and CT26 colon carcinoma cell lines. Moreover, in melanoma, TIGIT+ Tregs in TILs possess more suppressive functions compared with TIGIT- Tregs in TILs (Kurtulus et al. 2015). Intratumoral TIGIT+ T cells can be found in small-cell lung cancer, colorectal cancer, and melanoma (Chauvin et al. 2015; Johnston et al. 2014; Kurtulus et al. 2015).
Increased frequency of TIGIT+CD73-CD8+ T cells with a TOX+ TCF-1low profile in patients with newly diagnosed and relapsed AML
Published in OncoImmunology, 2021
F. Brauneck, F Haag, R. Woost, N. Wildner, E. Tolosa, A. Rissiek, G. Vohwinkel, J. Wellbrock, C. Bokemeyer, J. Schulze zur Wiesch, C. Ackermann, W. Fiedler
In agreement with other studies, we found that the frequency of PD-1+ cells was increased in patients during leukemia relapse, but also in remission.23 In pAML, however, we observed a significant elevation only for TIGIT on CD8+ T cells.6 TIGIT expression was explicitly related to the CD8+ effector memory T-cell subsets indicating that its expression is part of antigen-experience. TIGIT is expressed by dysfunctional T cells after chronic antigen stimulation in chronic infections and cancer.7,25 Regarding solid neoplasms, Chauvin et al. have demonstrated TIGIT upregulation on tumor antigen specific CD8+ T cells in the PB and tumor tissue of patients with advanced melanoma.25 Functionally, inhibition of the TIGIT or its ligands poliovirus receptor (PVR) and poliovirus receptor-related 2 (PVRL2) in T cells significantly enhanced in vitro cytotoxicity, and prolonged survival in AML mouse model in vivo.5 Importantly, high expression of PVR and PVRL2 was associated with a poorer prognosis in two independent AML patient cohorts, implying immune evasion in these patients.5 TIGIT+CD8+ T cells produced reduced levels of effector cytokines but showed a high proliferation and a high susceptibility to apoptosis, which were partially reverted by TIGIT knockdown.6 These results suggest that the TIGIT pathway is prominent in newly diagnosed AML, whereas multiple suppressive pathways contribute to leukemia relapse.
Desmoplastic small round cell tumor (DSRCT): emerging therapeutic targets and future directions for potential therapies
Published in Expert Opinion on Therapeutic Targets, 2020
Anastasia Loktev, Janet M. Shipley
Other cell surface proteins are mainly considered as immunotherapy targets but are also addressed with drug and radionuclide antibody conjugates. These include LRRC15, whose role for tumor progression is yet unclear. Poliovirus receptor (PVR, CD155) as well as PVR-related 2 (PVRL2, CD112) are both described as NK ligands [6]. Increased expression levels were also shown for the androgen receptor (AR, expressed in 59% of 35 DSRCT samples) and connective tissue growth factor CCN2, which is associated with the production of abundant extracellular matrix and may have autocrine or paracrine roles in disease progression [6,10]. However, expression levels vary widely, requiring thorough predictive patient stratification. Immune checkpoint inhibition by targeting CTLA-4 and PD-1 (CD279) was described as a potential novel therapeutic strategy for the treatment of DSRCT. However, despite PD-1 expression, expression of PD-L1 in DSRCT appears very limited. According to Bulbul et al., none of the patients in a recently described DSRCT cohort had identifiable tumoral PD-L1 expression [6,11].