CXCR4–CXCL12–CXCR7, TLR2–TLR4, and PD-1/PD-L1 in colorectal cancer liver metastases from neoadjuvant-treated patients

D’Alterio, Crescenzo; Nasti, Guglielmo; Polimeno, Marianeve; Ottaiano, Alessandro; Conson, Manuel; Circelli, Luisa; Botti, Giovanni; Scognamiglio, Giosuè; Santagata, Sara; Divitiis, Chiara De; Nappi, Anna; Napolitano, Maria; Tatangelo, Fabiana; Pacelli, Roberto; Izzo, Francesco; Vuttariello, Emilia; Botti, Gerardo; Scala, Stefania

doi:10.1080/2162402x.2016.1254313

Cited by 38 publications

(32 citation statements)

References 55 publications

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“…Multiple cancer cells show elevated expression of CXCR4, including breast, ovarian, and prostate cancer cells, melanomas, gliomas, neuroblastomas, osteosarcomas, leukemia, T-and B-cell lymphomas, colorectal, pancreatic, and uterine cancers, among others (Peled et al, 2012). ACKR3 expression is also increased in a number of cancer types including leukemia, breast, pancreatic, colon, and lung (Miao et al, 2007;Melo et al, 2014;D'Alterio et al, 2016;Guo et al, 2016). Both receptors are involved in different stages of tumorigenesis including growth, survival, and metastasis, according to in vitro and in vivo experimental data (Burns et al, 2006;Peled et al, 2012;Scholten et al, 2012;Teixidó et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Antibodies Targeting Chemokine Receptors CXCR4 and ACKR3

et al. 2019

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Dysregulation of the chemokine system is implicated in a number of autoimmune and inflammatory diseases, as well as cancer. Modulation of chemokine receptor function is a very promising approach for therapeutic intervention. Despite interest from academic groups and pharmaceutical companies, there are currently few approved medicines targeting chemokine receptors. Monoclonal antibodies (mAbs) and antibody-based molecules have been successfully applied in the clinical therapy of cancer and represent a potential new class of therapeutics targeting chemokine receptors belonging to the class of G protein-coupled receptors (GPCRs). Besides conventional mAbs, single-domain antibodies and antibody scaffolds are also gaining attention as promising therapeutics. In this review, we provide an extensive overview of mAbs, singledomain antibodies, and other antibody fragments targeting CXCR4 and ACKR3, formerly referred to as CXCR7. We discuss their unique properties and advantages over smallmolecule compounds, and also refer to the molecules in preclinical and clinical development. We focus on singledomain antibodies and scaffolds and their utilization in GPCR research. Additionally, structural analysis of antibody binding to CXCR4 is discussed. SIGNIFICANCE STATEMENT Modulating the function of GPCRs, and particularly chemokine receptors, draws high interest. A comprehensive review is provided for monoclonal antibodies, antibody fragments, and variants directed at CXCR4 and ACKR3. Their advantageous functional properties, versatile applications as research tools, and use in the clinic are discussed.

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Section: Introductionmentioning

confidence: 99%

Antibodies Targeting Chemokine Receptors CXCR4 and ACKR3

et al. 2019

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“…PD-L1, as a ligand for PD-1, is a transmembrane protein encoded by the Cd274 gene expressed on immune cells and tumor cells. It is not only a cancer-promoting factor in some certain malignant tumors such as hepatocellular carcinoma, gastric cancer and esophageal cancer; but also a protective factor in some other tumors including merkel cell carcinoma and breast cancer [19][20][21][22][23][24]. However, the mechanism of PD-L1 action in NPC is not clear.…”

Section: Discussionmentioning

confidence: 99%

PD-L1 associated with the expression of cancer cell-intrinsic PD-1 and p-S6 proteins and predicted a good prognosis in nasopharyngeal carcinoma

Zhang

Zheng

Zhan

et al. 2020

Preprint

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Aims: programmed cell death ligand 1 (PD-L1) is the ligand of programmed death 1 (PD-1) which is a host immunity inhibitory receptor. PD-L1 expressed in tumor cells has been widely discussed, while there is little research about tumor intrinsic-PD-1. P-S6 is an important downstream effector of the PI3K/AKT/mTOR pathway. This study aimed to investigate the expression of PD-L1 protein and its relationship with cancer cell-intrinsic PD-1 protein and p-S6 in nasopharyngeal carcinoma (NPC). Methods: the expression of PD-L1, PD-1 and p-S6 proteins in tissues of NPC, non-cancerous nasopharyngeal epithelia, primary lesions and matching metastases was detected by immunohistochemistry. Results: PD-L1, PD-1 and p-S6 expression and co-expression of PD-L1 and PD-1 proteins were significantly higher in NPC than those of in the non-cancerous nasopharyngeal epithelia, respectively (all P<0.05). Furthermore, there was evidently elevated expression of PD-1 and co-expression of PD-L1 and PD-1 in matched metastasis of NPC compared to their primary lesions (all P<0.01). Overall survival rate for NPC patients with positive expression of PD-L1 (P =0.035) was significantly higher than others. Multivariate Cox proportional hazard regression analysis identified that positive expression of PD-L1 (P=0.002) and p-S6 (P=0.003) were independent prognostic factors for NPC patients. Conclusions: positive expression of PD-L1 associated with expression of cancer cell-intrinsic PD-1 and p-S6, PD-L1 might be a good prognostic biomarker and p-S6 could serve as a valuable independent poor prognostic biomarker for NPC patients.

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“…As a ligand for PD-1, PD-L1 is a transmembrane protein expressed on immune cells and tumor cells encoded by the Cd274 gene. It is not only a cancerpromoting factor in some certain malignant tumors such as hepatocellular carcinoma, gastric cancer and esophageal cancer; also as protective factor in some other tumors including Merkel cell carcinoma and breast cancer [19][20][21][22][23][24]. However, the roles of PD-L1 action in NPC is not clear.…”

Section: Discussionmentioning

confidence: 99%

PD-L1 Associates with The Expression of Cancer Cell-Intrinsic PD-1 and p-S6 Proteins and Predicts A Good Prognosis in Nasopharyngeal Carcinoma

Zhang

Zheng²,

Zhan³

et al. 2020

Preprint

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Aims: programmed cell death ligand 1 (PD-L1) is the ligand of programmed death 1 (PD-1), which is a host immunity inhibitory receptor. Expression of PD-L1 in diverse tumor types has been widely discussed, while there is little research about tumor intrinsic-PD-1. P-S6 is an important downstream effector in the PI3K/AKT/mTOR pathway. Our study was focus on investigating PD-L1/PD-1/ p-S6 protein expression and aimed to illustrate their relationship in nasopharyngeal carcinoma (NPC). Methods: the expression of PD-1, PD-L1 and p-S6 proteins in tissues of NPC, non-cancerous nasopharyngeal epithelia, primary lesions and matching metastases was detected by immunohistochemistry. Results: PD-1, PD-L1 and p-S6 expression and co-expression of PD-1 and PD-L1 proteins were significantly higher in NPC than in the non-cancerous control tissue, respectively (all P<0.05). Furthermore, there was evidently elevated PD-1 expression and co-expression of PD-1 and PD-L1 in matched metastasis of NPC compared to their primary lesions (all P<0.01). NPC patients with positive expression of PD-L1 showed significantly higher overall survival rate than others (P =0.035). Multivariate Cox proportional hazard regression analysis confirmed that positive expression of PD-L1 and p-S6 were independent prognostic factors for NPC patients. Conclusions: positive expression of PD-L1 associates with expression of cancer cell-intrinsic PD-1 and p-S6, PD-L1 might serve as a good prognostic biomarker and p-S6 could be a valuable independent poor prognostic biomarker for NPC patients.

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CXCR4–CXCL12–CXCR7, TLR2–TLR4, and PD-1/PD-L1 in colorectal cancer liver metastases from neoadjuvant-treated patients

Cited by 38 publications

References 55 publications

Antibodies Targeting Chemokine Receptors CXCR4 and ACKR3

Antibodies Targeting Chemokine Receptors CXCR4 and ACKR3

PD-L1 associated with the expression of cancer cell-intrinsic PD-1 and p-S6 proteins and predicted a good prognosis in nasopharyngeal carcinoma

PD-L1 Associates with The Expression of Cancer Cell-Intrinsic PD-1 and p-S6 Proteins and Predicts A Good Prognosis in Nasopharyngeal Carcinoma

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