Abstract
The success of any given cancer immunotherapy relies on several key factors. In particular, success hinges on the ability to stimulate the immune system in a controlled and precise fashion, select the best treatment options and appropriate therapeutic agents, and use highly effective tools to accurately and efficiently assess the outcome of the immunotherapeutic intervention. Furthermore, a deep understanding and effective utilization of tumor-associated macrophages (TAMs), nanomedicine and biomedical imaging must be harmonized to improve treatment efficacy. Additionally, a keen appreciation of the dynamic interplay that occurs between immune cells and the tumor microenvironment (TME) is also essential. New advances toward the modulation of the immune TME have led to many novel translational research approaches focusing on the targeting of TAMs, enhanced drug and nucleic acid delivery, and the development of theranostic probes and nanoparticles for clinical trials. In this review, we discuss the key cogitations that influence TME, TAM modulations and immunotherapy in solid tumors as well as the methods and resources of tracking the tumor response. The vast array of current nanomedicine technologies can be readily modified to modulate immune function, target specific cell types, deliver therapeutic payloads and be monitored using several different imaging modalities. This allows for the development of more effective treatments, which can be specifically designed for particular types of cancer or on an individual basis. Our current capacities have allowed for greater use of theranostic probes and multimodal imaging strategies that have led to better image contrast, real-time imaging capabilities leveraging targeting moieties, tracer kinetics and enabling more detailed response profiles at the cellular and molecular levels. These novel capabilities along with new discoveries in cancer biology should drive innovation for improved biomarkers for efficient and individualized cancer therapy.
References
- 1 . World Cancer Report 2014. International Agency for Research on Cancer, France (2014).
- 2 . Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int. J. Cancer 132(5), 1133–1145 (2013).
- 3 The evaluation of NIR-absorbing porphyrin derivatives as contrast agents in photoacoustic imaging. Phys. Chem. Chem. Phys. 15(42), 18502–18509 (2013).
- 4 . Interlaced photoacoustic and ultrasound imaging system with real-time coregistration for ovarian tissue characterization. J. Biomed. Opt. 19(7), 76020 (2014).
- 5 . Real-time interlaced ultrasound and photoacoustic system for in vivo ovarian tissue imaging. Proc. SPIE 8581, Photons Plus Ultrasound: Imaging and Sensing 2013, 85814S.
doi:10.1117/12.2008273 , San Francisco, CA, USA, 4 March 2013. - 6 Imaging tumor hypoxia by near-infrared fluorescence tomography. J. Biomed. Opt. 16(6), 066009 (2011).
- 7 Target detection and characterization using a hybrid handheld diffuse optical tomography and photoacoustic tomography system. Proc. SPIE 7896, Optical Tomography and Spectroscopy of Tissue IX, 789614.
doi:10.1117/12.878913 , San Francisco, CA, USA, 1 March 2011. - 8 Target detection and quantification using a hybrid hand-held diffuse optical tomography and photoacoustic tomography system. J. Biomed. Opt. 16(4), 046010 (2011).
- 9 Targeting tumor hypoxia with 2-nitroimidazole-indocyanine green dye conjugates. J. Biomed. Opt. 18(6), 66009 (2013).
- 10 Target tumor hypoxia with 2-nitroimidazole-ICG dye conjugates. Proc. SPIE 8578, Optical Tomography and Spectroscopy of Tissue X, 85781Z.
doi:10.1117/12.2004767 , San Francisco, CA, USA, 25 March 2013. - 11 Hypoxia targeted carbon nanotubes as a sensitive contrast agent for photoacoustic imaging of tumors. Proc. SPIE 7899, Photons Plus Ultrasound: Imaging and Sensing 2011, 78991S.
doi:10.1117/12.878832 , San Francisco, CA, USA, 28 February 2011. - 12 Single wall carbon nanotube/bis carboxylic acid-ICG as a sensitive contrast agent for in vivo tumor imaging in photoacoustic tomography. Proc. SPIE 8581, Photons Plus Ultrasound: Imaging and Sensing 2013, 85814R.
doi:10.1117/12.2008179 , San Francisco, CA, USA, 4 March 2013. - 13 Photoacoustic imaging enhanced by indocyanine green-conjugated single-wall carbon nanotubes. J. Biomed. Opt. 18(9), 096006 (2013).
- 14 . Fluorescence imaging of vascular endothelial growth factor in mice tumors using targeted liposome ICG probe. Proc. SPIE 8578, Optical Tomography and Spectroscopy of Tissue X, 85782O.
doi:10.1117/12.20072968578 , San Francisco, CA, USA, 25 March 2013. - 15 . Enhanced fluorescence diffuse optical tomography with indocyanine green-encapsulating liposomes targeted to receptors for vascular endothelial growth factor in tumor vasculature. J. Biomed. Opt. 18(12), 126014 (2013).
- 16 Targeting tumor hypoxia: a third generation 2-nitroimidazole-indocyanine dye-conjugate with improved fluorescent yield. Org. Biomol. Chem. 13(46), 11220–11227 (2015).
- 17 Gold nanoparticle reprograms pancreatic tumor microenvironment and inhibits tumor growth. ACS Nano 10(12), 10636–10651 (2016).
- 18 Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues. Nat. Nanotechnol. 11(11), 986–994 (2016).
- 19 . Investigation on hydrophilicity of micro-arc oxidized TiO2 nano/micro-porous layers. Electrochim. Acta 55(20), 5786–5792 (2010).
- 20 . A facile method to grow V-doped TiO2 hydrophilic layers with nano-sheet morphology. Mater. Lett. 64(22), 2498–2501 (2010).
- 21 . One step growth of WO3-loaded Al2O3 micro/nano-porous films by micro arc oxidation. Colloid Surface A 355(1–3), 187–192 (2010).
- 22 Nanostructure sword-like ZnO wires: rapid synthesis and characterization through a microwave-assisted route. J. Alloys Compd. 469(1–2), 293–297 (2009).
- 23 . Microwave-assisted synthesis of narcis-like zinc oxide nanostructures. J. Alloys Compd. 497(1–2), 325–329 (2010).
- 24 Self-assembly of dandelion-like hydroxyapatite nanostructures via hydrothermal method. J. Am. Ceram. Soc. 91(10), 3292–3297 (2008).
- 25 Rapid formation of mono-dispersed hydroxyapatite nanorods with narrow-size distribution via microwave irradiation. J. Am. Ceram. Soc. 91(11), 3580–3584 (2008).
- 26 Boehmite nanopetals self assembled to form rosette-like nanostructures. Mater. Lett. 62(26), 4184–4186 (2008).
- 27 3D bundles of self-assembled lanthanum hydroxide nanorods via a rapid microwave-assisted route. J. Alloys Compd. 473(1–2), 283–287 (2009).
- 28 Self-assembly of ZnO nanoparticles and subsequent formation of hollow microspheres. J. Alloys Compd. 468(1–2), 303–307 (2009).
- 29 Ultrasonic induced photoluminescence decay in sonochemically obtained cauliflower-like ZnO nanostructures with surface 1D nanoarrays. Ultrason. Sonochem. 16(1), 11–14 (2009).
- 30 . Self-assembled zinc oxide nanostructures via a rapid microwave-assisted route. J. Cryst. Growth 310(15), 3621–3625 (2008).
- 31 . Structurally modified indocyanine dyes and targeting cancerous tumors. Abstr. Pap. Am. Chem. S 245(7), (2013).
- 32 Flower-like boehmite nanostructure formation in two-steps. J. Coord. Chem. 67(3), 555–562 (2014).
- 33 Self-assembly of boehmite nanopetals to form 3D high surface area nanoarchitectures. Appl. Phys. A 99(1), 317–321 (2010).
- 34 Hydrothermal synthesis and characterization of TiO2 nanostructures using LiOH as a solvent. Adv. Powder Technol. 22(3), 336–339 (2011).
- 35 CVD fabrication of carbon nanotubes on electrodeposited flower-like Fe nanostructures. J. Alloys Compd. 507(2), 494–497 (2010).
- 36 Influence of nano boehmite on solid state reaction of alumina and magnesia. J. Alloys Compd. 507(2), 443–447 (2010).
- 37 . Cellular constituents of immune escape within the tumor microenvironment. Cancer Res. 72(13), 3125–3130 (2012).
- 38 Heterogeneity of macrophage infiltration and therapeutic response in lung carcinoma revealed by 3D organ imaging. Nat. Commun. 8, 14293 (2017).
- 39 . The Yin-Yang of tumor-associated macrophages in neoplastic progression and immune surveillance. Immunol. Rev. 222, 155–161 (2008).
- 40 Macrophage ontogeny underlies differences in tumor-specific education in brain malignancies. Cell Rep. 17(9), 2445–2459 (2016).
- 41 CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat. Med. 19(10), 1264–1272 (2013).
- 42 . Macrophage plasticity and polarization: in vivo veritas. J. Clin. Invest. 122(3), 787–795 (2012).
- 43 Tumor-associated macrophages in glioma: friend or foe? J. Oncol. 2013, 486912 (2013).
- 44 . Tumor-induced myeloid deviation: when myeloid-derived suppressor cells meet tumor-associated macrophages. J. Clin. Invest. 125(9), 3365–3376 (2015).
- 45 . The role of microglia and macrophages in glioma maintenance and progression. Nat. Neurosci. 19(1), 20–27 (2015).
- 46 Tumor-associated microglia/macrophages enhance the invasion of glioma stem-like cells via TGF-beta1 signaling pathway. J. Immunol. 189(1), 444–453 (2012).
- 47 PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature 545(7655), 495–499 (2017).
- 48 . Resveratrol inhibits lung cancer growth by suppressing M2-like polarization of tumor associated macrophages. Cell. Immunol. 311, 86–93 (2017).
- 49 CD163+tumor-associated macrophage is a prognostic biomarker and is associated with therapeutic effect on malignant pleural effusion of lung cancer patients. Oncotarget 6(12), 10592–10603 (2015).
- 50 Dual targeted immunotherapy via in vivo delivery of biohybrid RNAi-peptide nanoparticles to tumor-associated macrophages and cancer cells. Adv. Funct. Mater. 25(27), 4183–4194 (2015).
- 51 Inhibition of CD47 effectively targets pancreatic cancer stem cells via dual mechanisms. Clin. Cancer Res. 21(10), 2325–2337 (2015).
- 52 Metformin reduces desmoplasia in pancreatic cancer by reprogramming stellate cells and tumor-associated macrophages. PLoS ONE 10(12), e0141392 (2015).
- 53 Targeting IL-17B-IL-17RB signaling with an anti-IL-17RB antibody blocks pancreatic cancer metastasis by silencing multiple chemokines. J. Exp. Med. 212(3), 333–349 (2015).
- 54 Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, Phase Ib trial. Lancet Oncol. 17(5), 651–662 (2016).
- 55 Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages. Nature 543(7645), 428–432 (2017).
- 56 Blockade of MMP14 activity in murine breast carcinomas: implications for macrophages, vessels, and radiotherapy. J. Natl Cancer Instit. 107(4), pii: djv017 (2015).
- 57 Inhibition of BMP signaling suppresses metastasis in mammary cancer. Oncogene 34(19), 2437–2449 (2015).
- 58 CCL2 and CCL5 are novel therapeutic targets for estrogen-dependent breast cancer. Clin. Cancer Res. 21(16), 3794–3805 (2015).
- 59 Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinoma. Cancer Lett. 360(2), 302–309 (2015).
- 60 Alternatively activated (M2) macrophages promote tumour growth and invasiveness in hepatocellular carcinoma. J. Hepatol. 62(3), 607–616 (2015).
- 61 Interleukin-34 promotes tumor progression and metastatic process in osteosarcoma through induction of angiogenesis and macrophage recruitment. Int. J. Cancer 137(1), 73–85 (2015).
- 62 Tasquinimod modulates suppressive myeloid cells and enhances cancer immunotherapies in murine models. Cancer Immunol. Res. 3(2), 136–148 (2015).
- 63 Periostin secreted by glioblastoma stem cells recruits M2 tumour-associated macrophages and promotes malignant growth. Nat. Cell Biol. 17(2), 170–182 (2015).
- 64 Ang-2/VEGF bispecific antibody reprograms macrophages and resident microglia to anti-tumor phenotype and prolongs glioblastoma survival. Proc. Natl Acad. Sci. USA 113(16), 4476–4481 (2016).
- 65 Anti-CD47 Treatment stimulates phagocytosis of glioblastoma by M1 and M2 polarized macrophages and promotes M1 polarized macrophages in vivo. PLoS ONE 11(4), e0153550 (2016).
- 66 Disrupting the CD47-SIRPα anti-phagocytic axis by a humanized anti-CD47 antibody is an efficacious treatment for malignant pediatric brain tumors. Sci. Transl. Med. 9(381), pii: eaaf2968 (2017).
- 67 . The role of myeloid cells in cancer therapies. Nat. Rev. Cancer 16(7), 447–462 (2016).
- 68 CD47-blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung cancer. J. Clin. Invest. 126(7), 2610–2620 (2016).
- 69 The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. Proc. Natl Acad. Sci. USA 109(17), 6662–6667 (2012).
- 70 In vivo imaging reveals a tumor-associated macrophage-mediated resistance pathway in anti-PD-1 therapy. Sci. Transl. Med. 9(389), pii: eaal3604 (2017).
- 71 . Nanoparticle-based magnetic resonance imaging on tumor-associated macrophages and inflammation. Front. Immunol. 8, 590 (2017).
- 72 . Nanomedicine(s) under the microscope. Mol. Pharm. 8(6), 2101–2141 (2011).
- 73 . Bridging the knowledge of different worlds to understand the big picture of cancer nanomedicines. Adv. Healthc. Mater.
doi:10.1002/adhm.201700432 (2017) (Epub ahead of print). - 74 . Nanomaterial-enabled cancer therapy. Mol. Ther.
doi:10.1016/j.ymthe.2017.04.026 (2017) (Epub ahead of print). - 75 . Cancer nanomedicine: progress, challenges and opportunities. Nat. Rev. Cancer 17(1), 20–37 (2017).
- 76 . The big picture on nanomedicine: the state of investigational and approved nanomedicine products. Nanomedicine 9(1), 1–14 (2013).
- 77 . Molecular imaging for personalized cancer care. Mol. Oncol. 6(2), 182–195 (2012).
- 78 . Molecular imaging: current status and emerging strategies. Clin. Radiol. 65(7), 500–516 (2010).
- 79 Hybrid PET-optical imaging using targeted probes. Proc. Natl Acad. Sci. USA 107(17), 7910–7915 (2010).
- 80 . Applications of nanoparticles in cancer medicine and beyond: optical and multimodal in vivo imaging, tissue targeting and drug delivery. Expert Opin. Drug Deliv. 12(12), 1837–1849 (2015).
- 81 . Surface modified multifunctional nanomedicines for simultaneous imaging and therapy of cancer. Bioimpacts 4(1), 3–14 (2014).
- 82 . Imaging biomarkers in immunotherapy. Biomark. Cancer 8(Suppl. 2), 1–13 (2016).
- 83 Size-dependent accumulation of particles in lysosomes modulates dendritic cell function through impaired antigen degradation. Intl. J. Nanomedicine 9, 3885–3902 (2014).
- 84 . Patents and nanomedicine. Nanomedicine (London, England) 2(3), 351–374 (2007).
- 85 . Strategies in the design of nanoparticles for therapeutic applications. Nat. Rev. Drug Discov. 9(8), 615–627 (2010).
- 86 . Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat. Biotechnol. 33(9), 941–951 (2015).
- 87 . Protein corona: opportunities and challenges. Int. J. Biochem. Cell Biol. 75, 143–147 (2016).
- 88 . The EPR effect for macromolecular drug delivery to solid tumors: improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv. Drug Deliv. Rev. 65(1), 71–79 (2013).
- 89 . Development of next-generation macromolecular drugs based on the EPR effect: challenges and pitfalls. Expert Opin. Drug Deliv. 12(1), 53–64 (2015).
- 90 Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth. Nat. Nanotechnol. 11(11), 977–985 (2016).
- 91 . Why the immune system should be concerned by nanomaterials? Front. Immunol. 8, 544 (2017).
- 92 . Advances toward more efficient targeted delivery of nanoparticles in vivo: understanding interactions between nanoparticles and cells. ACS Nano 11(3), 2397–2402 (2017).
- 93 . The intracellular destiny of the protein corona: a study on its cellular internalization and evolution. ACS Nano 10(11), 10471–10479 (2016).
- 94 . Secreted biomolecules alter the biological identity and cellular interactions of nanoparticles. ACS Nano 8(6), 5515–5526 (2014).
- 95 . The danger theory: 20 years later. Front. Immunol. 3, 287 (2012).
- 96 . It takes two to tango: understanding the interactions between engineered nanomaterials and the immune system. Eur. J. Pharm. Biopharm. 95(Pt A), 3–12 (2015).
- 97 . An X-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles. Nat. Mat. 5(2), 118–122 (2006).
- 98 . Enzymatically activatable diagnostic probes. Curr. Pharm. Biotechnol. 13(4), 523–536 (2012).
- 99 . Emerging applications for ferumoxytol as a contrast agent in MRI. J. Magn. Reson. Imaging 41(4), 884–898 (2015).
- 100 . Ferumoxytol use as an intravenous contrast agent for magnetic resonance angiography. Ann. Pharmacother. 45(12), 1571–1575 (2011).
- 101 . Molecular imaging in nanotechnology and theranostics. Mol. Imaging Biol.
doi:10.1007/s11307-017-1056-z (2017) (Epub ahead of print). - 102 Indocyanine green enhanced co-registered diffuse optical tomography and photoacoustic tomography. J. Biomed. Opt. 18(12), 126006 (2013).
- 103 NIR-driven smart theranostic nanomedicine for on-demand drug release and synergistic antitumour therapy. Sci. Rep. 5, 14258 (2015).
- 104 . Remotely triggered nano-theranostics for cancer applications. Nanotheranostics 1(1), 1–22 (2017).
- 105 . Stimuli-sensitive nanopreparations for combination cancer therapy. J. Control. Rel. 190, 352–370 (2014).
- 106 . Strategies for using nanoprobes to perceive and treat cancer activity: a review. J. Biol. Eng. 11, 13 (2017).
- 107 Nano-materials for gene therapy: an efficient way in overcoming challenges of gene delivery. J. Biosens. Bioelectron. 7(195), 12 (2016).
- 108 . Engineering nano- and microparticles to tune immunity. Adv. Mater. 24(28), 3724–3746 (2012).
- 109 . Efficient nanovaccine delivery in cancer immunotherapy. ACS Nano 11(3), 2387–2392 (2017).
- 110 Improved proliferation of antigen-specific cytolytic T lymphocytes using a multimodal nanovaccine. Intl. J. Nanomed. 11, 6103–6121 (2016).
- 111 . Radiolabeled nanoparticles for multimodality tumor imaging. Theranostics 4(3), 290–306 (2014).
- 112 Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe. Sci. Transl. Med. 6(260), 260ra149 (2014).
- 113 Preclinical development and clinical translation of a PSMA-targeted docetaxel nanoparticle with a differentiated pharmacological profile. Sci. Transl. Med. 4(128), 128ra139 (2012).
- 114 Reporter nanoparticle that monitors its anticancer efficacy in real time. Proc. Natl Acad. Sci. USA 113(15), E2104–E2113 (2016).
- 115 Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma. J. Clin. Invest. 121(7), 2768–2780 (2011).
- 116 Clinically-translated silica nanoparticles as dual-modality cancer-targeted probes for image-guided surgery and interventions. Integr. Biol. (Camb.) 5(1), 74–86 (2013).
- 117 . Intraoperative mapping of sentinel lymph node metastases using a clinically translated ultrasmall silica nanoparticle. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 8(4), 535–553 (2016).
- 118 [18F]CFA as a clinically translatable probe for PET imaging of deoxycytidine kinase activity. Proc. Natl Acad. Sci. USA 113(15), 4027–4032 (2016).
- 119 Novel PET probes specific for deoxycytidine kinase. J. Nucl. Med. 51(7), 1092–1098 (2010).
- 120 . Clinical experiences with systemically administered siRNA-based therapeutics in cancer. Nat. Rev. Drug Discov. 14(12), 843–856 (2015).
- 121 . siRNA delivery to the glomerular mesangium using polycationic cyclodextrin nanoparticles containing siRNA. Nucleic Acid Ther. 25(2), 53–64 (2015).
- 122 CRLX101 nanoparticles localize in human tumors and not in adjacent, nonneoplastic tissue after intravenous dosing. Proc. Natl Acad. Sci. USA 113(14), 3850–3854 (2016).
- 123 Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. Proc. Natl Acad. Sci. USA 103(16), 6315–6320 (2006).
- 124 Lipid nanoparticle assisted mRNA delivery for potent cancer immunotherapy. Nano Lett. 17(3), 1326–1335 (2017).
- 125 Synergy between surface and core entrapped metals in a mixed manganese–gadolinium nanocolloid affords safer MR imaging of sparse biomarkers. Nanomedicine 11(3), 601–609 (2015).
- 126 Dual-therapy with alphavbeta3-targeted Sn2 lipase-labile fumagillin-prodrug nanoparticles and zoledronic acid in the Vx2 rabbit tumor model. Nanomedicine 12(1), 201–211 (2016).
- 127 Accelerating the translation of nanomaterials in biomedicine. ACS nano 9(7), 6644–6654 (2015).
- 128 Treating brain tumor with microbeam radiation generated by a compact carbon-nanotube-based irradiator: initial radiation efficacy study. Radiat. Res. 184(3), 322–333 (2015).
- 129 Stationary chest tomosynthesis using a carbon nanotube x-ray source array: a feasibility study. Phys. Med. Biol. 60(1), 81–100 (2015).
- 130 Phase I first-in-human study of venetoclax in patients with relapsed or refractory non-hodgkin lymphoma. J. Clin. Oncol. 35(8), 826–833 (2017).
- 131 . Nanoparticle-based medicines: a review of FDA-approved materials and clinical trials to date. Pharm. Res. 33(10), 2373–2387 (2016).
- 132 . Engineered nanoparticles for biomolecular imaging. Nanoscale 3(8), 3007–3026 (2011).
- 133 . Fundamental limits of spatial resolution in PET. Nucl. Instrum. Methods Phys. Res. A 648(Suppl. 1), S236–S240 (2011).
- 134 Reporter gene imaging of targeted T cell immunotherapy in recurrent glioma. Sci. Transl. Med. 9(373), pii: eaag2196 (2017).
- 135 Practical immunoPET radiotracer design considerations for human immune checkpoint imaging. J. Nucl. Med.
doi:10.2967/jnumed.116.177659 (2016) (Epub ahead of print). - 136 Engineering high-affinity PD-1 variants for optimized immunotherapy and immuno-PET imaging. Proc. Natl Acad. Sci. USA 112(47), E6506–E6514 (2015).
- 137 An effective immuno-PET imaging method to monitor CD8-dependent responses to immunotherapy. Cancer Res. 76(1), 73–82 (2016).
- 138 . ImmunoPET imaging of murine CD4+ T cells using anti-CD4 Cys-diabody: effects of protein dose on T cell function and imaging. Mol. Imaging Biol.
doi:10.1007/s11307-016-1032-z (2016) (Epub ahead of print). - 139 Surface biotinylation of cytotoxic T lymphocytes for in vivo tracking of tumor immunotherapy in murine models. Cancer Immunol. Immunother. 65(12), 1545–1554 (2016).
- 140 . Quantitative CD3 PET imaging predicts tumor growth response to anti-CTLA-4 therapy. J. Nucl. Med. 57(10), 1607–1611 (2016).
- 141 . Microdosed lipid-coated (67)Ga-magnetite enhances antigen-specific immunity by image tracked delivery of antigen and CpG to lymph nodes. ACS Nano 10(1), 1602–1618 (2016).
- 142 Enhancing both CT imaging and natural killer cell-mediated cancer cell killing by a GD2-targeting nanoconstruct. J. Mater. Chem. B Mater. Biol. Med. 4(3), 513–520 (2016).
- 143 Nanomedicine for cancer immunotherapy: tracking cancer-specific T-cells in vivo with gold nanoparticles and CT imaging. ACS Nano 9(6), 6363–6372 (2015).
- 144 . Limits of tumor detectability in nuclear medicine and PET. Mol. Imaging Radionucl. Ther. 21(1), 23–28 (2012).
- 145 . Improved T(1)-weighted dynamic contrast-enhanced MRI to probe microvascularity and heterogeneity of human glioma. Magn. Reson. Imaging 25(9), 1292–1299 (2007).
- 146 Relative cerebral blood volume is a measure of angiogenesis in brain tuberculoma. J. Comput. Assist. Tomogr. 31(3), 335–341 (2007).
- 147 Dynamic contrast-enhanced magnetic resonance perfusion compared with digital subtraction angiography for the evaluation of extradural spinal metastases: a pilot study. Spine (Phila Pa 1976) 39(16), E950–E954 (2014).
- 148 Magnetic resonance imaging tracking of stem cells in vivo using iron oxide nanoparticles as a tool for the advancement of clinical regenerative medicine. Chem. Rev. 111(2), 253–280 (2011).
- 149 . Imaging single mammalian cells with a 1.5 T clinical MRI scanner. Magn. Reson. Med. 49(5), 968–971 (2003).
- 150 Advanced MRI assessment to predict benefit of anti-programmed cell death 1 protein immunotherapy response in patients with recurrent glioblastoma. Neuroradiology
doi:10.1007/s00234-016-1769-8 (2017) (Epub ahead of print). - 151 . In vivo magnetic resonance imaging of CD8+ T lymphocytes recruiting to glioblastoma in mice. Cancer Biother. Radiopharm. 31(9), 317–323 (2016).
- 152 Neuroimaging of peptide-based vaccine therapy in pediatric brain tumors: initial experience. Neuroimaging Clin. N. Am. 27(1), 155–166 (2017).
- 153 . Predicting clinical outcomes in chordoma patients receiving immunotherapy: a comparison between volumetric segmentation and RECIST. BMC Cancer 16(1), 672 (2016).
- 154 Using MRI to evaluate and predict therapeutic success from depot-based cancer vaccines. Mol. Ther. Methods Clin. Dev. 2, 15048 (2015).
- 155 Monitoring blood-brain barrier integrity following amyloid-beta immunotherapy using gadolinium-enhanced MRI in a PDAPP mouse model. J. Alzheimers Dis. 54(2), 723–735 (2016).
- 156 In vivo detection of amyloid plaques by gadolinium-stained MRI can be used to demonstrate the efficacy of an anti-amyloid immunotherapy. Front. Aging Neurosci. 8, 55 (2016).
- 157 Long-term intravital imaging of the multicolor-coded tumor microenvironment during combination immunotherapy. ELife 5, pii: e14756 (2016).
- 158 Enhanced immunotherapy of SM5–1 in hepatocellular carcinoma by conjugating with gold nanoparticles and its in vivo bioluminescence tomographic evaluation. Biomaterials 87, 46–56 (2016).
- 159 Retargeted human avidin-CAR T cells for adoptive immunotherapy of EGFRvIII expressing gliomas and their evaluation via optical imaging. Oncotarget 6(27), 23735–23747 (2015).
- 160 Allogenic dendritic cell and tumor cell fused vaccine for targeted imaging and enhanced immunotherapeutic efficacy of gastric cancer. Biomaterials 54, 177–187 (2015).
- 161 Near-infrared labeled, ovalbumin loaded polymeric nanoparticles based on a hydrophilic polyester as model vaccine: in vivo tracking and evaluation of antigen-specific CD8(+) T cell immune response. Biomaterials 37, 469–477 (2015).
- 162 Serial in vivo imaging using a fluorescence probe allows identification of tumor early response to cetuximab immunotherapy. Mol. Pharm. 12(1), 10–17 (2015).
- 163 Multimodal imaging analysis of an orthotopic head and neck cancer mouse model and application of anti-CD137 tumor immune therapy. Head Neck 38(4), 542–549 (2016).
- 164 Visualization of a primary anti-tumor immune response by positron emission tomography. Proc. Natl Acad. Sci. USA 102(48), 17412–17417 (2005).
- 165 . Immune-mediated disease in ipilimumab immunotherapy of melanoma with FDG PET-CT. Acad. Radiol. 24(1), 111–115 (2017).
- 166 . Primary mediastinal B-cell lymphoma – metabolic and anatomical features in 18FDG-PET/CT and response to therapy. Contemp. Oncol. (Pozn.) 20(4), 297–301 (2016).
- 167 Can interim 18F-FDG PET or diffusion-weighted MRI predict end-of-treatment outcome in FDG-avid MALT lymphoma after rituximab-based therapy?: a preliminary study in 15 patients. Clin. Nucl. Med. 41(11), 837–843 (2016).
- 168 In vivo tracking of phagocytic immune cells using a dual imaging probe with gadolinium-enhanced MRI and near-infrared fluorescence. ACS Appl. Mater. Interfaces 8(16), 10266–10273 (2016).
- 169 Magnetic enrichment of dendritic cell vaccine in lymph node with fluorescent-magnetic nanoparticles enhanced cancer immunotherapy. Theranostics 6(11), 2000–2014 (2016).
- 170 . Immunomodulatory function of the tumor suppressor p53 in host immune response and the tumor microenvironment. Int. J. Mol. Sci. 17, 1942 (2016).