Unmasking the expression of PD-L1 in Myeloid Derived Suppressor Cells: A case study in lung cancer to discover new drugs with specific on-target efficacy

•PD-L1 displays variation of spatial conformation in response to phorbol ester stimulation, which may confer a critical enhancement in binding affinity.•PD-L1 conformational change may be associated with an immunoregulatory mechanism that affects therapies targeting the PD-1/PD-L1 checkpoint.•Elimin...

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Published inTranslational oncology Vol. 14; no. 1; p. 100969
Main Authors Rico, Laura G., Aguilar Hernández, Andrés, Ward, Michael D., Bradford, Jolene A., Juncà, Jordi, Rosell, Rafael, Petriz, Jordi
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.01.2021
Neoplasia Press
Elsevier
Subjects
Flow cytometry
Immunotherapy
Letters to the Editor
MDSCs
PD-L1
PD-L1
Flow cytometry
MDSCs
Immunotherapy
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Abstract •PD-L1 displays variation of spatial conformation in response to phorbol ester stimulation, which may confer a critical enhancement in binding affinity.•PD-L1 conformational change may be associated with an immunoregulatory mechanism that affects therapies targeting the PD-1/PD-L1 checkpoint.•Eliminating MDSCs by promoting PD-L1 stabilized unfolded states on both PMN- and M-MDSCs could improve immunotherapy efficacy.•In view of these conformational properties, analysis of accumulation, expansion and survival of pathological immunosuppressive MDSCs could help to better understand and overcome the mechanisms of immunotherapy resistance, by developing new treatment strategies aimed at promoting PD-L1 stabilized unfolded states.
AbstractList •PD-L1 displays variation of spatial conformation in response to phorbol ester stimulation, which may confer a critical enhancement in binding affinity.•PD-L1 conformational change may be associated with an immunoregulatory mechanism that affects therapies targeting the PD-1/PD-L1 checkpoint.•Eliminating MDSCs by promoting PD-L1 stabilized unfolded states on both PMN- and M-MDSCs could improve immunotherapy efficacy.•In view of these conformational properties, analysis of accumulation, expansion and survival of pathological immunosuppressive MDSCs could help to better understand and overcome the mechanisms of immunotherapy resistance, by developing new treatment strategies aimed at promoting PD-L1 stabilized unfolded states.
• PD-L1 displays variation of spatial conformation in response to phorbol ester stimulation, which may confer a critical enhancement in binding affinity. • PD-L1 conformational change may be associated with an immunoregulatory mechanism that affects therapies targeting the PD-1/PD-L1 checkpoint. • Eliminating MDSCs by promoting PD-L1 stabilized unfolded states on both PMN- and M-MDSCs could improve immunotherapy efficacy. • In view of these conformational properties, analysis of accumulation, expansion and survival of pathological immunosuppressive MDSCs could help to better understand and overcome the mechanisms of immunotherapy resistance, by developing new treatment strategies aimed at promoting PD-L1 stabilized unfolded states.
ArticleNumber 100969
Author Ward, Michael D.
Bradford, Jolene A.
Rosell, Rafael
Petriz, Jordi
Rico, Laura G.
Juncà, Jordi
Aguilar Hernández, Andrés
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10.1016/j.cllc.2015.03.008
10.1016/j.coi.2018.03.009
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Keywords PD-L1
Flow cytometry
MDSCs
Immunotherapy
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• PD-L1 displays variation of spatial conformation in response to phorbol ester stimulation, which may confer a critical enhancement in binding affinity. •...
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SubjectTerms Flow cytometry
Immunotherapy
Letters to the Editor
MDSCs
PD-L1
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Title Unmasking the expression of PD-L1 in Myeloid Derived Suppressor Cells: A case study in lung cancer to discover new drugs with specific on-target efficacy
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