Nanoscale engagement of immune checkpoint inhibitor PD-L1 in membrane lipid rafts

Ruglioni, M.; Civita, S.; Salvadori, T.; Cristiani, S.; Carnicelli, V.; Barachini, S.; Petrini, I.; Diaspro, A.; Bianchini, P.; Storti, B.; Bizzarri, R.; Fogli, S.; Danesi, R.

doi:10.1101/2022.08.09.503318

bioRxiv · 10.1101/2022.08.09.503318

Nanoscale engagement of immune checkpoint inhibitor PD-L1 in membrane lipid rafts

Ruglioni, M.·Civita, S.·Salvadori, T.·Cristiani, S.·Carnicelli, V.·Barachini, S.·Petrini, I.·Diaspro, A.·Bianchini, P.·Storti, B.·Bizzarri, R.·Fogli, S.·Danesi, R.

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Abstract

Programmed death ligand 1 (PD-L1) plays a key role in several human tumors, and it has recently become a crucial target for cancer therapy. Yet, its subtle regulatory roles beside the well characterized immunosuppression in PD-1/PD-L1 immune checkpoint are still obscure and should be strictly related to its molecular properties in different cell settings. In this study we targeted the plasma membrane organization of PD-L1 in a Non-Small Cell Lung Cancer (NSCLC) cell line by a multiscale fluorescence imaging toolbox that included super-resolution microscopy approaches to reach the nanoscale. Our findings revealed for the first time that PD-L1 is prevalently engaged in the cholesterol-enriched "raft" regions of the cell membrane. Clusterization and engagement in membrane rafts may afford novel targets for the immuno-oncology strategies in the framework of NSCLC and, possibly, other tumor types.

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Ruglioni, M., Civita, S., Salvadori, T., Cristiani, S., Carnicelli, V., Barachini, S., Petrini, I., Diaspro, A., Bianchini, P., Storti, B., Bizzarri, R., Fogli, S., Danesi, R.. 2022-08-11. Nanoscale engagement of immune checkpoint inhibitor PD-L1 in membrane lipid rafts. https://doi.org/10.1101/2022.08.09.503318

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