June 2022

Diego de Miguel Perez, PhD; Fred Hirsch, MD, PhD; Philip Mack, PhD; Christian Rolfo, MD, PhD, and colleagues

Extracellular vesicle PD-L1 dynamics predict durable response to immune-checkpoint inhibitors and survival in patients with non-small cell lung cancer

Journal of Experimental & Clinical Cancer Research. 2022 Jun 2. PMID: 35650597

Based on growing evidence that extracellular vesicles (EVs) play an important role in tumor progression and tumor-immune interactions, Dr. Rolfo and colleagues evaluated whether EV PD-L1 expression could be used as a biomarker for prediction of durable treatment response and survival in patients with non-small cell lung cancer (NSCLC) undergoing treatment with immune-checkpoint inhibitors (ICIs). Findings indicate that the analysis of dynamic levels of PD-L1 in EVs could be used to stratify patients with advanced NSCLC who would derive benefit from ICIs and present better outcomes.

Press Release

Alice Kamphorst, PhD, is a recipient of a Distinguished Scholar Award from the Icahn School of Medicine at Mount Sinai for “Cellular Niches That Promote Effective Anti-tumor CD8 T Cell Responses.”

Christian Rolfo, MD, PhD, MBA, Dr.hc. was elected as a member of the Academy of Medical Sciences in Cordoba, Argentina, in recognition of his contributions to oncology and the field of liquid biopsy in cancer. Dr. Rolfo presented “Liquid Biopsy in Lung Cancer From Metastatic Disease to Cancer Interception” at the induction conference on May 26.

Cardinale Smith, MD, PhD, was accepted as a Fellow in the 2022-2023 Executive Leadership in Academic Health Care Program, a track of the Hedwig van Ameringen Executive Leadership in Academic Medicine (ELAM) program. The ELAM program is designed for senior women faculty who demonstrate potential for assuming executive leadership positions at academic health centers.

Richard Bakst, MD, has been appointed as Co-Chief of the Head and Neck Institute/Center of Excellence for Head and Neck Cancer. In this role, he will continue to collaborate with the multidisciplinary team to advance clinical care for patients with head and neck cancers, including cancers of the larynx, tongue, palate, sinuses, and thyroid. Dr. Bakst will also oversee radiation oncology research and related programs at the Institute.

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Sridevi Rajeeve, MD, Hematology and Medical Oncology fellow, received an ASCO Young Investigator Award from Conquer Cancer/the ASCO Foundation for “Feasibility Assessment of Wearable Device for Remote Monitoring and Immune Correlates of Patients With Multiple Myeloma Undergoing Chimeric Antigen Receptor T (CAR-T) Cell Therapy.” Samir Parekh, MBBS, is Dr. Rajeeve’s faculty mentor. Also, Dr. Rajeeve was one of four fellows accepted to the GRACE Patient Education Ambassadors Program for 2022-23.

Maria Soledad Sosa, PhD, received a 2022 Pershing Square Sohn Prize for Young Investigators in Cancer Research from the Pershing Square Sohn Cancer Research Alliance. The prize supports cancer researchers based in the greater New York City area and provides them with opportunities that encourage collaboration between academia and industry. Dr. Sosa and team will evaluate the spatial resolution and functional crosstalk of hundreds of barcoded disseminated cancer cells (DCCs) derived from early and late stages of cancer progression, and their interactions with innate immune cell microenvironments. By defining the clonal interactions between evolutionarily distinct types of DCCs and their immune niche, they will be able to identify novel pathways that can be pharmacologically targeted to stop life-threatening metastasis. 

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Eirini Papapetrou, MD, PhD, received R01 grant funding from the National Cancer Institute for “Impact of Mutational Order on Molecular Mechanisms of Oncogenesis.” The goal of the study is to investigate the role of the order of mutational acquisition in the clonal evolution of AML using genetic engineering of human induced pluripotent stem cells and primary human cells. 

Jose Javier Bravo-Cordero, PhD, has been awarded R03 grant funding from the National Cancer Institute for “Recording the Natural History of Cancer Progression Using a Crainbow Model of HER2+ Cancer.” Dr. Bravo-Cordero will conduct experiments using mouse models and high-resolution imaging during the course of tumor progression to define the homeostatic principles underlying the progression of breast cancer and dissect the role of HER2 isoforms on the metastatic cascade of breast tumors. Joshua Clair Snyder, PhD, Associate Professor of Surgery and Cell Biology at Duke University School of Medicine, is co-investigator on the grant.

Deanna Benson, PhD, and Emily Bernstein, PhD, received grant awards from the Melanoma Research Alliance.

Elvin Wagenblast, PhD, has joined Mount Sinai as Assistant Professor of Oncological Sciences and Pediatrics. His lab will develop and apply cutting-edge CRISPR/Cas9-mediated genome editing approaches in human primary blood stem cells to model and study childhood leukemia; the goal is to uncover insights into the genetic, cellular, and developmental mechanisms of childhood leukemia and identify therapeutic vulnerabilities of the disease. Dr. Wagenblast earned his PhD in Biological Sciences from the Cold Spring Harbor Laboratory School of Biological Sciences. He most recently was a Human Frontier Science Program Fellow and Banting Fellow in the laboratory of John Dick, PhD, FRS, at Princess Margaret Cancer Centre at the University of Toronto.

Triparna Sen, PhD, has joined Mount Sinai as Associate Professor of Oncological Sciences with a research focus on lung cancer. Dr. Sen earned her PhD in Cancer Biology from Jadaypur University in Kolkata, India, and a Master of Science in Genetics from the University of Calcutta. She did postdoctoral fellowships at MD Anderson Cancer Center and Washington University in St. Louis, and was most recently an assistant attending professor at Memorial Sloan Kettering Cancer Center. Dr. Sen is principal investigator on numerous federal and industry grants, including a current National Cancer Institute grant, “Targeting Replication Stress Signaling to Overcome Immune Evasion in Small Cell Lung Cancer.” Among her many awards and honors is the 2021 AAAS Martin and Rose Wachtel Cancer Research Award from the American Association for the Advancement of Science.

Daniel James Puleston, PhD, has joined Mount Sinai as Assistant Professor of Oncological Sciences. His laboratory research will focus on the role metabolism plays in cancer and the immune system. Dr. Puleston earned a Doctor of Philosophy in Immunology and a Master of Science in Integrated Immunology from the University of Oxford. He has received numerous awards, including a Sir Henry Wellcome Postdoctoral Fellowship from the Wellcome Trust and an EMBO Postdoctoral Fellowship from the European Molecular Biology Organization. Dr. Puleston was most recently a postdoctoral fellow at the Max Planck Institute of Immunobiology and Epigenetics, where he investigated polyamine metabolism in immune cell fate and function.

The Biorepository and Pathology Core (BPC), led by Rachel Brody, MD, PhD, oversees tissue/body fluid procurement, storage, and tracking from consented and de-identified specimens, and provides TCI members with access to normal tissue specimens and diseased tissue specimens from a broad array of diagnoses.

The BPC provides histology services that enable advanced analyses. These services include the capability to process, embed, and section fixed and frozen tissues (both animal and human) for the Mount Sinai Health System and the external academic and biopharmaceutical community.

Histology services include routine H&E staining as well as special stains for light microscopy. Single-plex and multi-plex immunohistochemistry, immunofluorescence, and in situ hybridization are also provided. Additionally, BPC offers full bright-field digital scanning capability with quantitative and qualitative digital image analysis provided through the HALO platform.

The BPC also offers laser capture microdissection, tissue microarray production, and DNA/RNA/miRNA extraction from fluids and tissue specimens (fixed and frozen) for downstream next generation sequencing.

Recent additions include:

• A second Ventana Discovery Ultra instrument for expanded immunostaining services
• New HALO AI analysis capacity

For more information, contact Dr. Brody at 212-241-0678 or Jerry Edward Chipuk, PhD, Associate Director of Basic Science Shared Resources at TCI.

Tzu-Yi Chen; Edgar Gonzalez-Kozlova, PhD; Taliah Soleymani; Sabrina La Salvia, PhD; Natasha Kyprianou, PhD; Susmito Sahoo, PhD; Ashutosh Tewari, MBBS; Carlos Cordon-Cardo, MD, PhD; Gustavo Stolovitzky, PhD; Navneet Dogra, PhD

Extracellular vesicles carry distinct proteo-transcriptomic signatures that are different from their cancer cell of origin

iScience. 2022 May 18.PMID: 35663013

Dr. Navneet Dogra and colleagues report that extracellular vesicles (EVs) enrich for distinct RNA and protein signatures that do not linearly correlate with their cell of origin. Their findings suggest that RNA-protein complexes may constitute a functional interaction network inside EVs to protect and regulate access to EV-RNA, until a function is achieved. The potential use of the integrative multi-omic proteo-transcriptomic platform to enhance the conceptual advance and diagnostic performance of diseases via liquid biopsy holds clinical significance.

Marta Łuksza, PhD, and colleagues

Neoantigen quality predicts immunoediting in survivors of pancreatic cancer

Nature. 2022 Jun 19. PMID: 35589842

To address whether immunoediting occurs naturally in human cancers, Dr. Łuksza and colleagues investigated how 70 human pancreatic cancers evolved over 10 years. They found that rare long-term survivors of pancreatic cancer who have stronger T cell activity in primary tumors develop genetically less heterogeneous recurrent tumors with fewer immunogenic mutations (neoantigens). They developed a model to predict how immune pressure induces cancer cell populations to evolve over time and suggest that the immune system fundamentally surveils host genetic changes to suppress cancer. Results support the idea of personalized vaccines for treatment of pancreatic cancer through stimulation of patients’ T cells. Looking ahead, this provides a rationale to use neoantigen-based therapies to activate immunity in pancreatic and similarly low-mutated cancers.

Robert J. Klein, PhD; Zeynep H. Gümüş, PhD

Are polygenic risk scores ready for the cancer clinic?—a perspective

Translational Lung Cancer Research. 2022 May.

In this review, Dr. Klein and Dr. Gümüş discuss the clinical utility of cancer polygenic risk scores (PRSs) for predicting personalized cancer risk. They contend that the clinical actions that can be taken in response to a PRS determine its clinical utility, and that this actionabilty depends on three aspects: (I) its discriminative power; (II) its performance in comparison to existing known risk factors; and (III) available preventive actions. They describe the strengths and challenges in each of these aspects for utilizing a PRS, as well as what is still needed to integrate cancer PRSs to the clinic. They also discuss the potential for using PRSs in precision oncology for personal prediction of disease progression or drug resistance in individuals with cancer.

Edward Kim, MD; Alex Sher, MD; Ghadi Abboud, MD; Myron Schwartz, MD; Marcel Facciuto, MD; Parissa Tabrizian, MD; Karin Knešaurek, PhD; Aaron Fischman, MD; Rahul Patel, MD; Scott Nowakowski, MD; Josep Llovet, MD; Barchir Taouli, MD: Robert Lookstein, MD

Radiation segmentectomy for curative intent of unresectable very early to early state hepatocellular carcinoma (RASER): a single-centre, single-arm study

The Lancet Gastroenterology & Hepatology. 2022 May 23. PMID: 35617978

This study found that radiation segmentectomy was efficacious, with a low proportion of high-grade adverse events in patients with unresectable very early to early stage hepatocellular carcinoma with suboptimal location for ablation. Results suggest that radiation segmentectomy should be further investigated as a potential curative treatment option for well selected patients.

Miguel A Martin-Serrano, PhD; Benjamin Kepecs; Alexander Tsankov, PhD; Daniela Sia, PhD, and colleagues 

Novel microenvironment-based classification of intrahepatic cholangiocarcinoma with therapeutic implications

Gut. 2022 May 18. PMID: 35584893



Dr. Daniela Sia and colleagues devised a comprehensive tumor microenvironment-based stratification of intrahepatic cholangiocarcinoma (iCCA). Findings provide key insights into the genotype-immunophenotype relationships of iCCA and identify potential tumor-intrinsic and extrinsic mechanisms of immunosuppression and evasion. Cross-species analysis establishes that the murine models align closely to human iCCA and are a valuable platform for the preclinical testing of combination therapeutic strategies. 

Nina Bickell, MD, and Amy Tiersten, MD, are featured in a Medscape video about breast cancer treatment, “Providing Equitable Care in Early Breast Cancer.”

Episode 1: New Therapies, New Treatments

Dr. Bickell

Dr. Tiersten

Sacha Gnjatic, PhD, presented a Distinguished Lecture at the 2nd Annual Research Symposium of the Division of Pathology and Laboratory Medicine at MD Anderson Cancer Center on May 13: “Immune Correlates of Cancer Immunotherapy From Tissues Using Single-Cell High-Dimensional Approaches.”

Marshall Posner, MD, participated in the induction of his protégé, Robert Haddad, MD, as the inaugural holder of the endowed McGraw Chair in Head and Neck Oncology at Dana-Farber Cancer Institute.

Dr. Posner is faculty mentor to Michael Wotman, MD, PGY3, who recently presented a poster—“Development of Glioblastoma Multiforme in Patients With Human Papillomavirus-associated Oropharyngeal Squamous Cell Carcinoma"—at the Department of Medicine Research Day 2022 on May 24.

All Research Day presentations can be found here. 

Faculty from the Center of Excellence for Multiple Myeloma presented at the International Myeloma Society’s workshop on immune effector cell therapies, held May 7 – 8 in Boston.

• Ajai Chari, MD: Non-BCMA Bispecifics and Other Novel Approaches
• Samir Parekh, MBBS: Profiling Multiple Myeloma and Immune Cells in CAR T Cell Therapy
• Cesar Rodriguez, MD: BCMA Bispecifics
• Oliver van Oekelen, MD: COVID-19 Vaccine Responses Post CAR T and Bispecific Antibody Therapy

Upcoming Presentations

TCI Seminar Series

Tuesday, June 21, 2022, Noon

Neil M. Iyengar, MD, Memorial Sloan Kettering Cancer Center

“Targeting Adiposity and Metabolic Perturbations to Improve Cancer Risk and Outcomes”

Institute for Genomic Heath Seminar Series

Tuesday, June 21, 2022, Noon

Lisa Bastarache, MS, Center for Precision Medicine, Vanderbilt University

“HER Data Qualtiy in Genetic Research: Why You Should Worry & What You Can Do About It”

Virtual Seminar on Gastrointestinal Cancer

Chaired by Deirdre Cohen, MD

Wednesday, June 29, 6:30 - 8 pm

Register at OncLive.com/events

Flyer

“Mammogram May" was launched this year to raise awareness of the importance of mammography in early breast cancer detection and treatment and encourage women to schedule an annual mammogram. “Our goal is to save lives, and this campaign will provide important messages and reminders to women: don’t put your health on hold, and take charge of your breast health,” said Elisa R. Port, MD, Chief of Breast Surgery and Director of the Dubin Breast Center.

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Blood Stem Cell Transplant Donor Registration Event

Conducted by Be The Match

Thursday, June 16, 10 am to 4 pm

Guggenheim Pavilion, Seventh Floor Atrium

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