September 2022

Bérengère Salomé, PhD; John Sfakianos, MD; Nina Bhardwaj, MD, PhD; Amir Horowitz, PhD; and colleagues

NKG2A and HLA-E define an alternative immune checkpoint axis in bladder cancer

Cancer Cell. 2022 Sept 12.

PMID: 36099881

This study shows that the natural killer cell inhibitory receptor NKG2A associates with improved survival and responsiveness to programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade immunotherapies in bladder tumors that have high abundance of CD8⁺ T cells. It provides a framework for subsequent clinical trials combining NKG2A blockade with other T cell-targeted immunotherapies, where tumors express higher levels of human leukocyte antigen (HLA)-E.

Press Release

The Ma'ayan Lab (PI, Avi Ma’ayan, PhD) and the Mount Sinai Center for Bioinformatics received grant funding from the National Cancer Institute (NCI) to continue the development of "ARCHS4: Massive Mining of Publicly Available RNA Sequencing Data," as part of NCI’s Informatics Technology for Cancer Research program. The project will develop algorithms and software to enhance the reuse of publicly available RNA-seq data and lead to identification of key molecular drivers as potential novel targets for the treatment of complex cancers.

Saghi Ghaffari MD, PhD, received renewal of her R01 grant from the National Cancer Institute, “Lysosomes and Their Communications With Mitochondria in Leukemic Stem Cell Disease Progression.” In this renewal, Dr. Ghaffari will use an organelle-based approach to select, characterize, and target the emerging leukemic stem cells and explore the effect of potential organelle alterations in old stem cells in promoting leukemia. The goal is to identify and test new therapeutic strategies to improve the outcome of patients with myeloid leukemias. 

Susanna Curtis, MD, PhD, received a loan repayment award from the National Heart, Lung, and Blood Institute through the National Institutes of Health Loan Repayment Program, designed to support highly qualified investigators starting in their research careers. 

Luis G. Rivera Sánchez, MD, has joined Mount Sinai as Assistant Professor of Surgery with a specialty in breast oncologic surgery. Dr. Rivera earned his MD at Ponce School of Medicine and Health Sciences in Puerto Rico. He completed internship and residency in General Surgery at Metropolitan Hospital Center, NYC Health and Hospitals, and fellowship in Breast Surgical Oncology at Fox Chase Cancer Center, Temple University Health System. Dr. Rivera also did a T-32 Postdoctoral Research Fellowship at Montefiore Medical Center/Albert Einstein College of Medicine. He sees patients at The Blavatnik Family Chelsea Medical Center at Mount Sinai.

Tara Balija, MD, has joined Mount Sinai as Assistant Professor of Surgery with a specialty in breast oncologic surgery. Dr. Balija earned her MD from the Icahn School of Medicine at Mount Sinai. She completed residency in General Surgery at Rutgers – Robert Wood Johnson Medical School and fellowship in Breast Surgical Oncology at Rutgers Cancer Institute of New Jersey. Dr. Balija practiced at Hackensack University Medical Center from 2015 until 2022; she also served as Director of the Breast Cancer Assessment and Risk Evaluation Program and Surgery Clerkship Site Director. Dr. Balija sees patients at Mount Sinai West.

Igor Bado, PhD, has joined Mount Sinai as Assistant Professor of Oncological Sciences, with a research focus on breast cancer metastasis. Dr. Bado earned a MS in Biochemistry and Applied Microbiology from the University of Ouagadougou in Burkina Faso and a PhD in Cell and Molecular Biology from the University of Houston. He did a postdoctoral fellowship in the laboratory of Xiang Zhang, PhD, at Baylor College of Medicine in Houston, where he most recently served as an Instructor at the Breast Center. Dr. Bado is Principal Investigator on breast cancer bone metastasis research, funded by the National Cancer Institute. Dr. Bado will serve as a Laureate with the Biomedical Laureates Program at the Icahn School of Medicine at Mount Sinai; the program is designed to increase diversity among basic and clinical research faculty and broaden mentorship opportunities.

Nina Bickell, MD, MPH, has been named a finalist for the C2 Catalyst for Equity Award, a Cancer Community Award. Finalists for this award have worked to overcome longstanding racial and ethnic disparities in cancer care.

Congratulations to TCI members who received 2022 Friedman Brain Institute Research Scholars awards:

• Priti Balchandani, PhD
• Emily Bernstein, PhD
• Dolores Hambardzumyan, PhD, MBA
• Hongyan Zou, MD, PhD

The 2022 awards support 17 investigators across 10 departments and showcase research approaches marked by innovation and collaboration.

The Tisch Cancer Institute proudly partnered with the Center in Excellence for Youth Education (CEYE) this past summer in support of programming for high school students whose backgrounds are underrepresented in medicine, with the goal of increasing diversity. 

TCI lab investigators who are interested in hosting a student for a full-year or summer and inspiring them to pursue careers in cancer are encouraged to contact Janice Gabrilove, MD, or Dan Hasson, PhD. 

Read the Full Article Here 

The Human Immune Monitoring Center (HIMC) provides access to a comprehensive suite of immune monitoring assays allowing for the quantification of circulating proteins and immune cell characterization, along with spatial organization in tissues to support basic science, clinical, and translational studies.

Miriam Merad, MD, PhD, directs the HIMC. Sacha Gnjatic, PhD, is Associate Director and Seunghee Kim-Schulze, PhD, is Facility Director.

Recent additions:

• Multiplexed Immunohistochemical Consecutive Staining on Single Slide (MICSSS) services have been expanded with the addition of an Ionpath Multiplexed Ion Beam Imaging Tissue Analyzer.

• A new Olink^® Signature Q100 enables readout of Olink^® Target 96/48 and Olink^® Focus protein biomarker panels using small volumes.

• The single-cell RNA-seq workflow now includes enhanced quality control and the 10X Genomics data processing pipeline.

• Computational pipelines were upgraded to run in parallel on Minerva or on Amazon Web Services as Dockerized batch jobs, and the data can be shared securely with researchers via cloud-based tools (e.g., AWS, GitHub, Mount Sinai Box).



For more information, contact Dr. Gnjatic (sacha.gnjatic@mssm.edu) or Jerry Edward Chipuk, PhD, Associate Director of Basic Science Shared Resources at TCI.

Tarek Mouhieddine, MD; Oliver Van Oekelen, MD, PhD; Samir Parekh, MD; and colleagues

Sequencing T-cell redirection therapies leads to deep and durable responses in relapsed/refractory myeloma patients

Blood Advances. 2022 Aug 27. PMID: 36018226

In this manuscript the authors report, for the first time, the feasibility of sequencing T-cell redirection therapies with chimeric antigen receptor (CAR)-T cells and bispecific antibodies for heavily pretreated relapsed/refractory multiple myeloma patients. They found that sequential use of different T-cell redirection therapies can lead to deep and durable responses following relapse after bispecific antibody therapy.

Press Release

Hearn Jay Cho, MD, PhD; Sacha Gnjatic, PhD; Samir Parekh, MD; and colleagues



High dimensional immune profiling of smoldering multiple myeloma distinguishes distinct tumor microenvironments

Clinical Lymphoma, Myeloma and Leukemia. 2022 Jul 16. PMID: 35945129

This study investigated the interactions between abnormal clonal plasma cells and the tumor microenvironment (TM) in smoldering multiple myeloma via high dimensional immunologic analysis of bone marrow specimens. Results suggest that the continuum from precursor conditions to active multiple myeloma does not consist of a single pathway in the TME, and that complex interactions between myeloma cells and the TME may ultimately determine progression and inform clinical management.

Matthew Lin; Judit Svensson-Arvelund, PhD; Gabrielle Lubitz; Brian Brown, PhD; Joshua Brody, MD; and colleagues



Cancer vaccines: the next immunotherapy frontier

Nature Cancer. 2022 Aug 23. PMID: 35999309

This review develops a novel classification system for cancer vaccines, focusing on what is known of the included antigens, which tumors express those antigens, and where the antigens colocalize with antigen-presenting cells. The authors thus delineate: predefined vaccines (shared or personalized) and anonymous vaccines (ex vivo or in situ). The review highlights the need for accurate immune monitoring of early trials to acknowledge failures and advance the most promising vaccines.

Samantha Platt, MD; Guy H. Montgomery, PhD; Julie Schnur, PhD; Laurie Margolies, MD

BI-RADS-0 screening mammography: Risk factors that prevent or delay follow-up time to diagnostic evaluation

Journal of the American College of Radiology.

2022 Aug 16. PMID: 25985631

This retrospective study aimed to identify risk factors for delayed follow-up from BI-RADS-0 screening mammogram. Of 4,552 individuals included, 904 (19.9 percent) had no follow-up. Findings showed that individuals who identify as Black, Asian, or Hispanic are at increased risk for delayed follow-up. Further study will identify the causes for these delays in order to better guide interventions to reduce the care disparities for these individuals.

Philip C. Mack, PhD; Fred R. Hirsch, MD, PhD; and colleagues

Circulating tumor DNA (ctDNA) kinetics predict progression-free and overall survival in EGFR TKI-treated patients with EGFR-mutant NSCLC (SWOG S1403)

Clinical Cancer Research. 2022 Sept 1. PMID: 35713632

This study showed that early treatment-associated changes in mutant EGFR circulating tumor DNA levels were highly predictive of long-term outcome for patients with non-small cell lung cancer treated on the SWOG S1403 trial, in which all patients had EGFR E19del or L858R mutations in tumor tissue, were EGFR TKI-naïve, and received the second-generation EGFR TKI afatinib with or without cetuximab. Findings from this prospective study provide the basis for incorporation of plasma ctDNA kinetics into new clinical concepts in development at SWOG and Mount Sinai.

Virginia Corbett, MD, and colleagues

Evolving role of seneca valley virus and its biomarker TEM8/ANTXR1 in cancer therapeutics

Frontiers in Molecular Biosciences. 2022 Aug 26. PMID: 36090051

In this review, the authors discuss the oncolytic virus Seneca Valley Virus, which specifically targets cells with neuroendocrine properties, and its therapeutic implications. They discuss relevant preclinical and clinical data involving the Seneca Valley Virus and how bio-selecting for TEM8/ANTXR1, a negative tumor prognosticator, can lead to first of its kind biomarker driven oncolytic viral cancer therapy.

John Grout; Helene Salmon, PhD; Miriam Merad, MD, PhD; and colleagues

Spatial positioning and matrix programs of cancer-associated fibroblasts promote T cell exclusion in human lung tumors

Cancer Discovery. 2022 Aug 26. PMID: 36027053

This study describes two cancer-associated fibroblast (CAF) populations associated with T cell exclusion in human lung cancer. It demonstrates the importance of pairing molecular and spatial analysis of the tumor microenvironment in order to develop novel CAF targeting strategies that augment response to cancer immunotherapies.

Scott Friedman, MD, will deliver the Keynote Address at a New York Academy of Sciences scientific symposium, October 14 at the Boston Public Library, in conjunction with the 2022 Innovators in Science Award (to be presented to Dr. Jeffrey Gordon and Dr. Elaine Hsiao). Dr. Friedman’s address will focus on the challenges and opportunities presented by a research career in gastroenterology and liver diseases.

Philip Mack, PhD, presented an oral abstract at the IASLC 2022 World Conference on Lung Cancer.

 “Serological Response to SARS-CoV-2 Vaccination in Patients With Lung Cancer: Preliminary Results From a Prospective Matched Controlled Study” can be found on pages 32-33 of the Abstract Book.

Upcoming Seminars

TCI Seminar Series

Tuesday, September 20, 12 pm

William R. Sellers, MD

Harvard Medical School/Dana Farber Cancer Institute/Broad Institute

"The Discovery of Context Specific Paralog Dependence in Cancer

Through Combinatorial CRISPR Screens"

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Conference on Screening for Lung Cancer and

Research for Early Lung Cancer Treatment

Wednesday - Friday, September 21 - 23

In-person and Virtual

Agenda

Register

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TCI Translational Oncology Seminar

Thursday, September 22, 8:30 am

Samuel Sidi, PhD

"A Non-canonical IRAK Signaling Pathway

Triggered by Ionizing Radiation"

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TCI Seminar Series

Tuesday, September 27, 12 pm

Triparna Sen, PhD

"Novel Insights and Therapeutic Strategies for

Recalcitrant Subsets of Lung Cancer"

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Cancer Biology Retreat

Department of Oncological Sciences

Monday, October 3, 8:30 am - 5 pm

The Ruth and Harold D. Uris Center for Education

The Metropolitan Museum of Art

Register

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OncLive State of the Science Summit: Multiple Myeloma

Ajai Chari, MD, Chair

Wednesday, October 12, 6 -9 pm

New York Hilton Midtown | 1335 6th Avenue

Register

Oncology specialists led by Kai Tsao, MD—part of a 40+ member team of healthcare experts from the Mount Sinai Health System—met on August 17 with the healthcare minister of Guyana to begin a dedicated process of improving oncology services in Guyana’s public healthcare system.

Pictured left to right: Munir Ghesani, MD; Kai Tsao, MD; Guyana Minister of Health Frank Anthony, MD; Kenneth Rosenzweig, MD; Shaina Sidnauth, MHA; Amar Dhanraj, MHA