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6. PD-L1 in tumor microenvironment mediates resistance to oncolytic immunotherapy

Author

Zamarin, Dmitriy, Ricca, Jacob M., Sadekova, Svetlana, Oseledchyk, Anton, Yu, Ying, Blumenschein, Wendy M., Wong, Jerelyn, Gigoux, Mathieu, Merghoub, Taha, and Wolchok, Jedd D.

Subjects
Care and treatment, Usage, Research, Patient outcomes, Tumors -- Drug therapy -- Analysis -- Health aspects -- Care and treatment -- Patient outcomes -- Research, Immunotherapy -- Analysis -- Health aspects -- Usage -- Patient outcomes -- Research
Abstract

Introduction In the past 60 years, multiple studies have evaluated the antitumor potential of oncolytic viruses (OVs), and while promising activity has been demonstrated in a variety of animal models, [...], Intralesional therapy with oncolytic viruses (OVs) leads to the activation of local and systemic immune pathways, which may present targets for further combinatorial therapies. Here, we used human tumor histocultures as well as syngeneic tumor models treated with Newcastle disease virus (NDV) to identify a range of immune targets upregulated with OV treatment. Despite tumor infiltration of effector T lymphocytes in response to NDV, there was ongoing inhibition through programmed death ligand 1 (PD-L1), acting as a mechanism of early and late adaptive immune resistance to the type I IFN response and T cell infiltration, respectively. Systemic therapeutic targeting of programmed cell death receptor 1 (PD- 1) or PD-L1 in combination with intratumoral NDV resulted in the rejection of both treated and distant tumors. These findings have implications for the timing of PD-1/PD-L1 blockade in conjunction with OV therapy and highlight the importance of understanding the adaptive mechanisms of immune resistance to specific OVs for the rational design of combinatorial approaches using these agents.

Published
2018
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8. Application of a 21-Gene Recurrence Score in a Swiss Single-Center Breast Cancer Population: A Comparative Analysis of Treatment Administration before and after TAILORx.

Author

Chiru, Elena Diana, Oseledchyk, Anton, Schoetzau, Andreas, Kurzeder, Christian, Mosimann, Raphael, Vetter, Marcus, and Grašič Kuhar, Cvetka

Subjects
*HORMONE receptor positive breast cancer, *BREAST cancer, *HORMONE receptors, *HORMONE therapy, *COMPARATIVE studies, *YOUNG women
Abstract

In patients with hormone receptor positive, human epidermal receptor 2 negative (HR+/HER2−) negative breast cancer (BC), the TAILORx study showed the benefit of adding chemotherapy (CHT) to endocrine therapy (ET) in a subgroup of patients under 50 years with an intermediate Oncotype DX recurrence score (RS 11–25). The aim of the present study was to determine if the TAILORx findings, including the changes in the RS categories, impacted CHT use in the intermediate RS (11–25) group in daily practice, as well as to identify the main factors for CHT decisions. We conducted a retrospective study on 326 BC patients (59% node-negative), of which 165 had a BC diagnosis before TAILORx (Cohort A) and 161 after TAILORx publication (Cohort B). Changes in the RS categories led to shifts in patient population distribution, thereby leading to a 40% drop in the low RS (from 60% to 20%), which represented a doubling in the intermediate RS (from 30% to 60%) and an increase of 5% in the high RS (from 8–10% to 15%). The overall CHT recommendation and application did not differ significantly between cohort B when compared with A (19% vs. 22%, resp., p = 0.763). In the intermediate RS (11–25), CHT use decreased by 5%, while in the high-risk RS category (>25), there was an increase of 13%. The tumor board recommended CHT for 90% of the patients according to the new RS guidelines in cohort A and for 85% in cohort B. The decision for CHT recommendation was based on age (OR 0.93, 95% CI 0.08–0.97, p = 0.001), nodal stage (OR 4.77, 95% CI 2.03–11.22, p < 0.001), and RS categories (RS 11–25 vs. RS 0–10: OR 0.06 (95% CI 0.02–0.17), p < 0.001; RS > 26 vs. RS 11–25: OR 618.18 95% CI 91.64–4169.91, p < 0.001), but did not depend on the cohort. In conclusion, while the tumor board recommendation for CHT decreased in the intermediate RS category, there was an increase being reported in the high RS category, thus leading to overall minor changes in CHT application. As expected, among the younger women with intermediate RS and unfavorable histopathological factors, CHT use increased. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Abstract 5217: Defining the balance of anti-viral and anti-tumor T cell responses to oncolytic virus therapy using single cell approaches

Author

Burman, Bharat, primary, Ceglia, Nicholas, additional, Hirschhorn, Daniel, additional, Budhu, Sadna, additional, Mangarin, Levi, additional, Oseledchyk, Anton, additional, Bykov, Yonina, additional, McPherson, Andrew, additional, Shah, Sohrab, additional, Wolchok, Jedd, additional, Merghoub, Taha, additional, and Zamarin, Dmitriy, additional

Published
2022
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13. Multiplexed molecular imaging with surface enhanced resonance Raman scattering nanoprobes reveals immunotherapy response in mice via multichannel image segmentation

Author

Andreou, Chrysafis, primary, Plakas, Konstantinos, additional, Berisha, Naxhije, additional, Gigoux, Mathieu, additional, Rosch, Lauren E., additional, Mirsafavi, Rustin, additional, Oseledchyk, Anton, additional, Pal, Suchetan, additional, Zamarin, Dmitriy, additional, Merghoub, Taha, additional, Detty, Michael R., additional, and Kircher, Moritz F., additional

Published
2022
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15. Surgical ovarian suppression for adjuvant treatment in hormone receptor positive breast cancer in premenopausal patients

Author

Oseledchyk, Anton, primary, Gemignani, Mary L, additional, Zhou, Qin C, additional, Iasonos, Alexia, additional, Elahjji, Rahmi, additional, Adamou, Zara, additional, Feit, Noah, additional, Goldfarb, Shari B, additional, Long Roche, Kara, additional, Sonoda, Yukio, additional, Goldfrank, Deborah J, additional, Chi, Dennis S, additional, Saban, Sally S, additional, Broach, Vance, additional, Abu-Rustum, Nadeem R, additional, Carter, Jeanne, additional, Leitao, Mario, additional, and Zivanovic, Oliver, additional

Published
2020
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16. Surface-enhanced Resonance Raman Scattering Nanoprobe Ratiometry for Detecting Microscopic Ovarian Cancer via Folate Receptor Targeting

Author

Andreou, Chrysafis, Oseledchyk, Anton, Nicolson, Fay, Berisha, Naxhije, Pal, Suchetan, Kircher, Moritz F., and Andreou, Chrysafis [0000-0002-3464-9110]

Subjects
General Chemical Engineering, Nanoprobe, 02 engineering and technology, Spectrum Analysis, Raman, Sensitivity and Specificity, Article, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, Peritoneal cavity, symbols.namesake, Recurrence, Cell Line, Tumor, medicine, Animals, Humans, Nanotechnology, Stage (cooking), 030304 developmental biology, Ovarian Neoplasms, 0303 health sciences, General Immunology and Microbiology, business.industry, General Neuroscience, Folate Receptors, GPI-Anchored, Cancer, 021001 nanoscience & nanotechnology, medicine.disease, medicine.anatomical_structure, Folate receptor, Cancer research, symbols, Female, Molecular imaging, 0210 nano-technology, Ovarian cancer, business, Raman spectroscopy
Abstract

Ovarian cancer represents the deadliest gynecologic malignancy. Most patients present at an advanced stage (FIGO stage III or IV), when local metastatic spread has already occurred. However, ovarian cancer has a unique pattern of metastatic spread, in that tumor implants are initially contained within the peritoneal cavity. This feature could enable, in principle, the complete resection of tumor implants with curative intent. Many of these metastatic lesions are microscopic, making them hard to identify and treat. Neutralizing such micrometastases is believed to be a major goal towards eliminating tumor recurrence and achieving long-term survival. Raman imaging with surface enhanced resonance Raman scattering nanoprobes can be used to delineate microscopic tumors with high sensitivity, due to their bright and bioorthogonal spectral signatures. Here, we describe the synthesis of two 'flavors' of such nanoprobes: an antibody-functionalized one that targets the folate receptor — overexpressed in many ovarian cancers — and a non-targeted control nanoprobe, with distinct spectra. The nanoprobes are co-administered intraperitoneally to mouse models of metastatic human ovarian adenocarcinoma. All animal studies were approved by the Institutional Animal Care and Use Committee of Memorial Sloan Kettering Cancer Center. The peritoneal cavity of the animals is surgically exposed, washed, and scanned with a Raman microphotospectrometer. Subsequently, the Raman signatures of the two nanoprobes are decoupled using a Classical Least Squares fitting algorithm, and their respective scores divided to provide a ratiometric signal of folate-targeted over untargeted probes. In this way, microscopic metastases are visualized with high specificity. The main benefit of this approach is that the local application into the peritoneal cavity — which can be done conveniently during the surgical procedure — can tag tumors without subjecting the patient to systemic nanoparticle exposure. False positive signals stemming from non-specific binding of the nanoprobes onto visceral surfaces can be eliminated by following a ratiometric approach where targeted and non-targeted nanoprobes with distinct Raman signatures are applied as a mixture. The procedure is currently still limited by the lack of a commercial wide-field Raman imaging camera system, which once available will allow for the application of this technique in the operating theater. 145

Published
2019
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17. Multiplexed molecular imaging with surface enhanced resonance Raman scattering nanoprobes reveals immunotherapy response in mice viamultichannel image segmentationElectronic supplementary information (ESI) available: Online Methods, Fig. S1–S10 and Tables S1, S2. See DOI: https://doi.org/10.1039/d2nh00331g

Author

Andreou, Chrysafis, Plakas, Konstantinos, Berisha, Naxhije, Gigoux, Mathieu, Rosch, Lauren E., Mirsafavi, Rustin, Oseledchyk, Anton, Pal, Suchetan, Zamarin, Dmitriy, Merghoub, Taha, Detty, Michael R., and Kircher, Moritz F.

Abstract

Visualizing the presence and distribution of multiple specific molecular markers within a tumor can reveal the composition of its microenvironment, inform diagnosis, stratify patients, and guide treatment. Raman imaging with multiple molecularly-targeted surface enhanced Raman scattering (SERS) nanoprobes could help investigate emerging cancer treatments preclinically or enable personalized treatment assessment. Here, we report a comprehensive strategy for multiplexed imaging using SERS nanoprobes and machine learning (ML) to monitor the early effects of immune checkpoint blockade (ICB) in tumor-bearing mice. We used antibody-functionalized SERS nanoprobes to visualize 7 + 1 immunotherapy-related targets simultaneously. The multiplexed images were spectrally resolved and then spatially segmented into superpixels based on the unmixed signals. The superpixels were used to train ML models, leading to the successful classification of mice into treated and untreated groups, and identifying tumor regions with variable responses to treatment. This method may help predict treatment efficacy in tumors and identify areas of tumor variability and therapy resistance.

Published
2022
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18. Intraoperative hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer

Author

Oseledchyk, Anton and Zivanovic, Oliver

Subjects
Care and treatment, Methods, Ovarian cancer -- Complications and side effects -- Care and treatment, Hyperthermic intraperitoneal chemotherapy -- Methods
Abstract

Introduction Ovarian cancer causes more deaths than any other gynecologic malignancy, accounting for 14,180 deaths in the United States annually, and with a prevalence of 21,290 new cases estimated for [...], Ovarian cancer, because it is largely confined to the peritoneal cavity, has a unique tumor biology and metastatic spread pattern. Its metastatic potential comes from detached tumor cells in the peritoneal cavity that re-attach to the mesothelial lining of the peritoneal surface. It is proposed that these micrometastases without neovasculature, as well as floating malignant cells, are drivers of early recurrence, since they can be neither resected nor adequately treated by systemic chemotherapy. This represents the major rationale for local treatment by means of postoperative intraperitoneal (IP) chemotherapy, which is the standard of care in the United States in patients with advanced-stage ovarian cancer who have minimal residual disease following cytoreductive surgery. An alternative locoregional treatment strategy is the 'HIPEC' procedure--hyperthermic IP chemoperfusion that is performed during the operation immediately following completion of gross tumor resection, and which provides improved tissue penetration and distribution of the chemotherapeutics. However, prospective data are limited and an outcomes benefit has yet to be shown. Here we discuss the advantages and pitfalls of HIPEC, as well as current data and ongoing prospective trials.

Published
2015

26. Approach to the sonographic evaluation of fetal ventriculomegaly at 11 to 14 weeks gestation

Author

Manegold-Brauer, Gwendolin, Oseledchyk, Anton, Floeck, Anne, Berg, Christoph, Gembruch, Ulrich, Geipel, Annegret, Manegold-Brauer, Gwendolin, Oseledchyk, Anton, Floeck, Anne, Berg, Christoph, Gembruch, Ulrich, and Geipel, Annegret

Abstract

Background: The aim of the study was to report the prevalence and associated findings of fetal ventriculomegaly between 11 + 0 and 13 + 6 gestational weeks and to evaluate a sonographic approach to classify first trimester ventriculomegaly in the standard axial plane used for biparietal diameter (BPD) measurement. Methods: The ratio between choroid plexus and lateral ventricle diameter (PDVDR), between the choroid plexus and lateral ventricle length (PLVLR) and between the choroid plexus and lateral ventricle area (PAVAR) were calculated from stored 2D images of the axial head plane in 100 normal fetuses and 17 fetuses with ventriculomegaly. Results: The PDVDR, the PLVLR and the PAVAR were below the 5(th) percentile in 82.4 %, 94.1 % and 94.1 % of the cases with ventriculomegaly. Ventriculomegaly was isolated in 29.4 % and associated with further anomalies in 70.6 % at the initial evaluation. The mean PLVLR in euploid compared to aneuploid fetuses was significantly lower (0.40 versus 0.53 (p = 0.0332)). Conclusions: The measurements of PDVDR, PLVLR and PAVAR are helpful to objectify ventriculomegaly at 11-14 gestational weeks. The PLVLR and PAVAR were superior to PDVDR, since there seems to be rather shrinkage of the choroid plexus than an increased width of the lateral ventricles in the first trimester.

Published
2016

27. Impact of Extended Primary Surgery on Suboptimally Operable Patients With Advanced Ovarian Cancer

Author

Oseledchyk, Anton, primary, Hunold, Lena Elisa, additional, Mallmann, Michael R., additional, Domröse, Christian M., additional, Abramian, Alina, additional, Debald, Manuel, additional, Kaiser, Christina, additional, Kiefer, Nicholas, additional, Putensen, Christian, additional, Pantelis, Dimitrios, additional, Fimmers, Rolf, additional, Kuhn, Walther, additional, Schäfer, Nico, additional, and Keyver-Paik, Mignon-Denise, additional

Published
2016
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28. Imaging of Liver Tumors Using Surface-Enhanced Raman Scattering Nanoparticles

Author

Andreou, Chrysafis, primary, Neuschmelting, Volker, additional, Tschaharganeh, Darjus-Felix, additional, Huang, Chun-Hao, additional, Oseledchyk, Anton, additional, Iacono, Pasquale, additional, Karabeber, Hazem, additional, Colen, Rivka R., additional, Mannelli, Lorenzo, additional, Lowe, Scott W., additional, and Kircher, Moritz F., additional

Published
2016
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31. Correction: Multiplexed molecular imaging with surface enhanced resonance Raman scattering nanoprobes reveals immunotherapy response in mice viamultichannel image segmentation

Author

Andreou, Chrysafis, Plakas, Konstantinos, Berisha, Naxhije, Gigoux, Mathieu, Rosch, Lauren E., Mirsafavi, Rustin, Oseledchyk, Anton, Pal, Suchetan, Zamarin, Dmitriy, Merghoub, Taha, Detty, Michael R., and Kircher, Moritz F.

Abstract

Correction for ‘Multiplexed molecular imaging with surface enhanced resonance Raman scattering nanoprobes reveals immunotherapy response in mice viamultichannel image segmentation’ by Chrysafis Andreou et al., Nanoscale Horiz., 2022, 7, 1540–1552, https://doi.org/10.1039/d2nh00331g.

Published
2023
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32. Correction: Multiplexed molecular imaging with surface enhanced resonance Raman scattering nanoprobes reveals immunotherapy response in mice via multichannel image segmentation.

Author

Andreou C, Plakas K, Berisha N, Gigoux M, Rosch LE, Mirsafavi R, Oseledchyk A, Pal S, Zamarin D, Merghoub T, Detty MR, and Kircher MF

Abstract

Correction for 'Multiplexed molecular imaging with surface enhanced resonance Raman scattering nanoprobes reveals immunotherapy response in mice via multichannel image segmentation' by Chrysafis Andreou et al. , Nanoscale Horiz. , 2022, 7 , 1540-1552, https://doi.org/10.1039/d2nh00331g.

Published
2023
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