Preclinical immunoPET/CT imaging using Zr-89-labeled anti-PD-L1 monoclonal antibody for assessing radiation-induced PD-L1 upregulation in head and neck cancer and melanoma

Kikuchi, Masahiro; Clump, David A.; Srivastava, Raghvendra M.; Sun, Lingyi; Zeng, Dexing; Díaz-Pérez, Julio A.; Anderson, Carolyn J.; Edwards, Wilson B.; Ferris, Robert L.

doi:10.1080/2162402x.2017.1329071

Cited by 85 publications

(75 citation statements)

References 37 publications

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“…297,309,310 Accumulating evidence suggest indeed that metronomic chemotherapy and hypofractionated radiation (rather than chemotherapy at the MTD and high single-dose radiation) exerts superior immunostimulatory (and hence therapeutic, at least in some settings) effects. [311][312][313][314] Alongside, it will be important to devise highly efficient combinatorial regimens that harness not only the ability of some treatments to drive ICD, but also the off-target immunostimulatory effects of a variety of agents. We are convinced that conventional therapeutic regimens -if properly employed -are a very powerful and relatively economical tool to drive clinically relevant anticancer immune responses.…”

Section: Discussionmentioning

confidence: 99%

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

et al. 2017

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The expression "immunogenic cell death" (ICD) refers to a functionally unique form of cell death that facilitates (instead of suppressing) a T cell-dependent immune response specific for dead cell-derived antigens. ICD critically relies on the activation of adaptive responses in dying cells, culminating with the exposure or secretion of immunostimulatory molecules commonly referred to as "damage-associated molecular patterns". Only a few agents can elicit bona fide ICD, including some clinically established chemotherapeutics such as doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin. In this Trial Watch, we discuss recent progress on the development of ICD-inducing chemotherapeutic regimens, focusing on studies that evaluate clinical efficacy in conjunction with immunological biomarkers.

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Section: Discussionmentioning

confidence: 99%

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

et al. 2017

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“…Kikuchi et al also investigated the effect of radiotherapy on the expression of PD-L1. A 89 Zr-labeled mAb against mouse PD-L1 was used to show increased tracer uptake in a syngeneic head and neck tumor model after fractionated radiotherapy (Kikuchi et al 2017). Other research teams have also successfully employed mAbs for imaging of PD-L1 using different radionuclides, including 89 Zr, 111 In, 64 Cu and 131 I (Hettich et al 2016;Chatterjee et al 2016;Josefsson et al 2016;Nedrow et al 2017aNedrow et al , 2017bLesniak et al 2016;Li et al 2018;Moroz et al 2018;Truillet et al 2018;Pang et al 2018).…”

Section: Pd-l1 Imagingmentioning

confidence: 99%

Tracers for non-invasive radionuclide imaging of immune checkpoint expression in cancer

Wierstra

Sandker

Aarntzen

et al. 2019

EJNMMI radiopharm. chem.

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Immunotherapy with checkpoint inhibitors demonstrates impressive improvements in the treatment of several types of cancer. Unfortunately, not all patients respond to therapy while severe immune-related adverse effects are prevalent. Currently, patient stratification is based on immunotherapy marker expression through immunohistochemical analysis on biopsied material. However, expression can be heterogeneous within and between tumor lesions, amplifying the sampling limitations of biopsies. Analysis of immunotherapy target expression by noninvasive quantitative molecular imaging with PET or SPECT may overcome this issue. In this review, an overview of tracers that have been developed for preclinical and clinical imaging of key immunotherapy targets, such as programmed cell death-1, programmed cell death ligand-1, IDO1 and cytotoxic T lymphocyteassociated antigen-4 is presented. We discuss important aspects to consider when developing such tracers and outline the future perspectives of molecular imaging of immunotherapy markers.

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“…The effects of RT on tumor microenvironment and its interaction with tumor immunity is a complex balance of suppressing and activating signals [27]. Sufficient evidence has shown that RT might enhanced the therapeutic effects of anti-PD-1/PD-L1 agents in HNSCC [28], however, many questions remain regarding how RT affects tumor immunity in hypopharyngeal cancer.…”

Section: Discussionmentioning

confidence: 99%

The role of GLUT-1 in upregulation of PD-L1 expression after radiotherapy and PD-L1 is associated with a favourable overall survival in hypopharyngeal cancer

Shen

Zhou

2020

Preprint

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KEYWORDSglucose transporter 1, programmed cell death ligand 1, radiotherapy, prognosis, hypopharyngeal cancer 2 Abstract Purpose: Although the alteration of tumor immunity after radiotherapy (RT) has been studied widely in recent years, how radiotherapy mediates tumor immunity and whether glycolysis is involved in the mediation in hypopharyngeal cancer are still unclear. This study aimes to determine whether radiotherapy regulates programmed cell death ligand 1( PD-L1) partly via glucose transporter 1(GLUT-1) expression and whether PD-L1 expression predicts overall survival (OS) in patients with hypopharyngeal cancer.Methods: PD-L1, Glut-1 expression and C D4+, CD8+ T cell were detected by immunohistochemistry analysis on 47 pre-RT and 25 post-RT specimens of hypopharyngeal cancer. The changes of these indicators before and after radiotherapy were compared, and their association with overall survival of patients were analyzed. Moreover, we used siRNA-GLUT-1 to inhibit GLUT-1 expression and determined whether GLUT-1 was a key factor involved in mediation of PD-L1 expression by RT in vitro. Results: In multivariate analysis, patients with higher PD-L1 expression (P=0.037), higher CD4+ T cell infiltration (P=0.016) and earlier clinical stage (P=0.019) had favourable OS. The PD-L1 expression and CD4+, CD8+ T cell increased significantly after RT. PD-L1 expression was correlated with Glut-1 in pre-RT (P=0.002), but not after-RT(P=0.051). The PD-L1 expression of FaDu cells was upregulated after RT, especially at 96h after RT in vitro. However, the PD-L1 expression of siRNA-GLUT-1 FaDu cells was significantly decreased at 96h after RT when compared with FaDu cells. Conclusion: The patients with high PD-L1 expression and CD4+ T cell infiltration might have favourable OS in hypopharyngeal cancer. RT could increase PD-L1 expression and alter tumor immunity, the expression of PD-L1 was correlated with Glut-1, and inhibiting GLUT-1 expression might decrease the expression of PD-L1. GLUT-1 might participate in the alteration of tumor immunity after RT.

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Preclinical immunoPET/CT imaging using Zr-89-labeled anti-PD-L1 monoclonal antibody for assessing radiation-induced PD-L1 upregulation in head and neck cancer and melanoma

Cited by 85 publications

References 37 publications

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

Tracers for non-invasive radionuclide imaging of immune checkpoint expression in cancer

The role of GLUT-1 in upregulation of PD-L1 expression after radiotherapy and PD-L1 is associated with a favourable overall survival in hypopharyngeal cancer

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