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Multimodal Multiplexed Immunoimaging with Nanostars to Detect Multiple
Immunomarkers and Monitor Response to Immunotherapies.
Authors Ou YC, Wen X, Johnson CA, Shae D, Ayala OD, Webb JA, Lin EC, DeLapp RC, Boyd KL,
Richmond A, Mahadevan-Jansen A, Rafat M, Wilson JT, Balko JM, Tantawy MN,
Vilgelm AE, Bardhan R
Submitted By Submitted Externally on 9/28/2020
Status Published
Journal ACS nano
Year 2020
Date Published 1/1/2020
Volume : Pages 14 : 651 - 663
PubMed Reference 31851488
Abstract The overexpression of immunomarker programmed cell death protein 1 (PD-1) and
engagement of PD-1 to its ligand, PD-L1, are involved in the functional
impairment of cluster of differentiation 8+ (CD8+) T cells, contributing to
cancer progression. However, heterogeneities in PD-L1 expression and
variabilities in biopsy-based assays render current approaches inaccurate in
predicting PD-L1 status. Therefore, PD-L1 screening alone is not predictive of
patient response to treatment, which motivates us to simultaneously detect
multiple immunomarkers engaged in immune modulation. Here, we have developed
multimodal probes, immunoactive gold nanostars (IGNs), that accurately detect
PD-L1+ tumor cells and CD8+ T cells simultaneously in vivo, surpassing the
limitations of current immunoimaging techniques. IGNs integrate the whole-body
imaging of positron emission tomography with high sensitivity and multiplexing
of Raman spectroscopy, enabling the dynamic tracking of both immunomarkers. IGNs
also monitor response to immunotherapies in mice treated with combinatorial
PD-L1 and CD137 agonists and distinguish responders from those nonresponsive to
treatment. Our results showed a multifunctional nanoscale probe with
capabilities that cannot be achieved with either modality alone, allowing
multiplexed immunologic tumor profiling critical for predicting early response
to immunotherapies.


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