July 2023

Assaf Magen, PhD; Pauline Hamon, PhD; Thomas Marron, MD, PhD; Alice Kamphorst, PhD; Miriam Merad, MD, PhD; and colleagues

Intratumoral dendritic cell-CD4⁺ T helper cell niches enable CD8⁺ T cell differentiation following PD-1 blockade in hepatocellular carcinoma

Nature Medicine. 2023 June 15. PMID: 37322116

Despite no apparent defects in T cell priming and recruitment to tumors, a large subset of T cell rich tumors fail to respond to immune checkpoint blockade (ICB). Dr. Merad, Dr. Kamphorst, Dr. Marron and team leveraged a neoadjuvant anti-PD-1 trial in patients with hepatocellular carcinoma (HCC) to explore correlates of response to ICB within T cell-rich tumors. They discovered that a specific niche of immune cells in tumors may be critical for reactivating exhausted T cells and enabling them to attack liver tumors upon treatment with checkpoint blockade. The study shows that killer CD8 T cells are only reactivated when in close proximity to two other immune cell types: dendritic cells, which educate CD8 T cells to recognize cancer cells, and helper CD4 T cells, which aid in activating the CD8 T cells. Results reveal the presence of cellular triads within tumor lesions consisting of mregDC, CXCL13⁺ T_H and PD-1^hi Progenitor CD8⁺ T cells, and suggest that these triads are critical for the differentiation of Progenitor CD8⁺ T cells into effective antitumor CD8⁺ T cells upon PD-1 blockade.

Press Release

Rima Patel, MD, joined the Division of Hematology and Medical Oncology as Assistant Professor on July 1. Dr. Patel’s clinical practice will focus on breast medical oncology and she will serve as Medical Director for Breast Geriatric Oncology; as such, she will develop a new program to improve treatment and care for elderly patients with breast cancer. Dr. Patel will see patients at the Dubin Breast Center and The Blavatnik Family Chelsea Medical Center.

Dr. Patel completed her fellowship in Hematology and Medical Oncology at the Icahn School of Medicine at Mount Sinai, serving as Chief Fellow in 2022-2023. She did residency training in Internal Medicine at Tufts Medical Center and earned her MD from Rutgers Robert Wood Johnson Medical School. Dr. Patel is leading several research projects and developing investigator-initiated protocols in breast cancer. She is the recipient of a 2023 Conquer Cancer Merit Award.

John Sfakianos, MD, was selected for the 2023-2024 Leadership Emerging in Academic Departments (LEAD) Program. This innovative NIH/National Center for Advancing Translational Sciences-funded year-long program, currently in its fifth year, was developed by Janice Gabrilove, MD, to propel self-awareness and self-management skills, catalyze leadership capacity, and advance new career and networking opportunities among talented junior faculty from varied basic, translational, and clinical scientific and medical disciplines and diverse backgrounds.

• Curriculum
• Related Publication

For questions about the program, contact Dr. Gabrilove.

Josep Llovet, MD, PhD, was nominated at the European Association for the Study of the Liver Congress, held June 21-24 in Vienna, as Editor-in-Chief of the Journal of Hepatology Reports. Dr. Llovet’s full term will begin January 1, 2024. The journal publishes articles on global issues in hepatology, with a focus on clinical trials, novel diagnostics, precision medicine and therapeutics, cellular and molecular research, cancer, microbiome, systems biology, epidemiology, and biotechnology advances and devices. 

Nina Bhardwaj, MD, PhD, served on the Organizing Committee for the Japanese Cancer Association/American Association for Cancer Research Precision Cancer Medicine International Conference, held June 28-30 in Japan. Dr. Bhardwaj also opened the conference session on Advances in T-cell Biology.

Nicholas Gulati, MD, PhD, received the 2023 ASA Daneen & Charles Stiefel Investigative Scientist Award for Melanoma Research from the American Skin Association for “Use of Topical Diphencyprone to Improve Efficacy of Checkpoint Inhibition in Melanoma Patients.” The award supports an investigator-initiated phase I clinical trial at Mount Sinai that is actively recruiting patients (https://clinicaltrials.gov/study/NCT05481658).

Jose Javier Bravo-Cordero, PhD, received a R61 grant award from the National Cancer Institute for “Intersectional Genetics-Based Biosensors for Dormant Cancer Cells.” The goal of the project is to devise a dormant cancer cell biosensor by using intersectional genetics and synthetic biology technologies that will allow the identification, molecular profiling, and genetic manipulation of dormant cancer cells in vivo.

Fred Hirsch, MD, PhD, and Adolfo Garcia-Sastre, PhD, received continuation of funding for their U54 grant from the National Cancer Institute ($3.2 million for 18 months beginning September 1, 2023), to further investigate the factors contributing to the vulnerability of SARS-CoV-2 infection in patients with lung cancer through serological analysis of antibody response, and to characterize and compare the antibody response to SARS-CoV-2 infection or SARS-CoV-2 vaccines in patients with lung cancer to a matched “healthy” control group.

The TCI Flow Cytometry Shared Resource (FCSR) provides access to state-of-the-art technologies, services, and expertise in flow cytometry to enhance scientific discovery, interaction, and productivity that are essential to innovative cancer research programs. The FCSR is directed by Jordi Ochando, PhD; Guillermo Villegas, PhD, serves as Assistant Core Operations Manager.

The FCSR recently welcomed two new members: Alessandro Marins Dos Santos, PhD, and Jovvian Parakkal, PhD, as Senior Scientists to support the flow cytometry needs of TCI members. Dr. Marins has more than 15 years of experience at flow cytometry core facilities, including the Oswaldo Cruz Foundation in Rio de Janeiro, the Albert Einstein Education and Research Center in São Paulo, and most recently the Flow Cytometry Resource Center at Rockefeller University. Dr. Parakkal, an immunologist, has applied novel flow cytometric approaches to investigate the host’s immune responses to immunization and infections. He has expertise in data analysis and the ImageStream Mark II imaging flow cytometer. 

In terms of equipment enhancement, the core has acquired a new cell sorter, the BD Symphony S6, featuring 5 lasers and 50 detectors. It is temporarily located at the Icahn Medical Institute, Room 13-7, where it is being used to sort mouse and fixed human cells. Once moved to its final location, the BD Symphony S6 will be enclosed inside a biosafety hood to isolate infected mouse cells and cells from human origin.

For further information, visit the FCSR site or contact Jerry Edward Chipuk, PhD, Associate Director of Basic Science Shared Resources at TCI.  

Subhamoy Chakraborty, PhD; Charles Coleman, BS; Deniz Demircioglu, PhD; Dan Hasson, PhD; Triparna Sen, PhD; and colleagues

De novo and histologically transformed small cell lung cancer is sensitive to lurbinectedin treatment through the modulation of EMT and NOTCH signaling pathways

Clinical Cancer Research. 2023 Jun 29. PMID: 37382635

Small cell lung cancer (SCLC) is a poorly immunogenic, high-grade neuroendocrine carcinoma that has an exceptionally poor prognosis. Lurbinectedin, conditionally approved as a second-line treatment for metastatic SCLC, drives clinical responses in about 35% of patients, highlighting the need to develop improved mechanistic insight and predictive biomarkers of response. In this study, Dr. Sen and colleagues determine the efficacy of lurbinectedin in a comprehensive panel of SCLC cell lines and patient-derived xenografts. Furthermore, they demonstrate that lurbinectedin, either as a single agent or in combination with osimertinib, causes a remarkable anti-tumor response in multiple models of EGFR-mutant lung adenocarcinoma with histologic transformation to SCLC. This study provides mechanistic insight into lurbinectedin response in SCLC and the first demonstration that lurbinectedin is a potential therapeutic target after SCLC transformation.

Burak Ucpinar, MD; Ketan Badani, MD; and colleagues

Robot-assisted partial nephrectomy for complex renal tumors: Analysis of a large multi-institutional database

Urologic Oncology. 2023 Jun 12. PMID: 37316415

This study assessed the outcomes and determined the safety and feasibility of robotic partial nephrectomy RPN for complex renal masses. Based on evaluation of 372 patients, Dr. Badani and team determined that RPN is a safe and reproducible procedure for complex tumors with R.E.N.A.L. Nephrometry scores ≥10. Results suggest excellent rates of trifecta (negative margin, low ischemia time, and no complications) achievement and short-term functional outcomes. Long-term oncological and functional evaluation are needed to further support this conclusion.

Madison Weber; Minh Nguyen, PhD; Meng Yen Li, PhD; Pooja Flora, PhD; Masahiro Shuda, PhD; Elena Ezhkova, PhD



Merkel cell plyomavirus T-antigen-medicated reprogramming in adult merkel cell progenitors

Journal of Investigative Dermatology. 2023 May 29. PMID: 37257637

Understanding Merkel cell regeneration is of interest to the study of Merkel cell carcinoma (MCC), a rare neuroendocrine skin cancer hypothesized to originate in a Merkel cell progenitor transformed by Merkel cell polyomavirus (MCV) small (sT-Ag) and large (LT-Ag) T-antigens. Dr. Ezhkova and team sought to understand what the adult Merkel cell progenitors are and whether they can give rise to MCC. They show that SOX9⁺ cells not only give rise to Merkel cells postnatally but can also be reprogrammed by MCV T antigens to express neuroendocrine markers and form hyperproliferative lesions. Results offer insights into Merkel cell biology and implicate SOX9⁺ Merkel cell progenitors as a potential origin of MCC.

Sharonne Holtzman, MD; Guillaume Stoffels, PhD; Matt Flint, MD; Caitlin Carr, MD; Monica Prasad-Hayes, MD; Kresten Zeligs, MD; Stephanie Blank, MD

Outcomes for patients with high-risk endometrial cancer undergoing sentinel lymph node assessment versus full lymphadenectomy

Gynecologic Oncology. 2023 Jun 2. PMID: 37270906



The objective of this study was to determine the progression free survival (PFS) and overall survival (OS) among patients with high-risk endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping and dissection compared to patients who underwent pelvic +/- para-aortic lymphadenectomy (LND). Based on a cohort of 189 patients, findings showed no significant difference in oncologic outcomes in patients with high-risk EC staged with SLN evaluation compared to LND and no difference in PFS or OS. The data support the safety of SLN evaluation in patients with high-risk EC.

Md Kabir, PhD; Ning Sun, PhD; Ramon Parsons, MD, PhD; Jian Jin, PhD; and colleagues

Acetylation targeting chimera enables acetylation of the tumor suppressor p53

Journal of the American Chemical Society. 2023 Jun 26. PMID: 37365684



Drs. Jin and Parsons and team developed a novel technology, termed Acetylation Targeting Chimera (AceTAC), for inducing targeted acetylation of proteins of interest. Applying this technology to target the tumor suppressor p53, the team discovered MS78, the first AceTAC of the p53 Y220C mutant, which effectively acetylated p53Y220C and suppressed proliferation and clonogenicity of cancer cells harboring the p53Y220C mutation with little toxicity in cancer cells with wild-type p53 and normal cells. This novel AceTAC technology could provide a generalizable platform for targeting proteins, such as tumor suppressors, via acetylation.

Diana Kang, BS; Haoyuan Li, MD, EngD; Yizhou Dong, PhD

Advancements of in vitro transcribed mRNA (IVT mRNA) to enable translation into the clinics

Advanced Drug Delivery Reviews. 2023 Jun 14. PMID: 37321375

This article focuses on the various structural elements of the mRNA that affect its properties to serve as a therapeutic modality and how the synthesis of in vitro transcribed mRNA supports this effort. Dr. Dong and team summarize several types of RNAs that may further expand their various therapeutic applications to diseases such as cancer.

Scott Friedman, MD, gave the Keynote Presentation—“Perspectives on Cirrhosis”—at the Japan Society of Hepatology meeting in Nara, Japan, on June 15.

The Department of Otolaryngology-Head and Neck Surgery at the Icahn School of Medicine at Mount Sinai had more than 10 oral presentations and 13 poster presentations at the American Head and Neck Society’s International Conference on Head and Neck Cancer, July 8-12, in Montreal. Graduating Chief Resident Rocco Ferrandino, MD, presented “Performance Metrics of TTMV-HPV DNA Serologic Testing for the Diagnosis and Surveillance of Human Papillomavirus-Associated Oropharyngeal Cancer” (oral) and “Circulating HPV Tumor DNA Testing in Patients Presenting with an Indeterminate Lateral Neck Mass: A Prospective Trial” (poster). Dr. Ferrandino will do a fellowship at the University of Washington. Brandon Gold, medical student at Icahn Mount Sinai, presented a poster, “Survival Outcomes for High-Risk HPV Genotypes in Oropharyngeal Squamous Cell Carcinoma,” on investigating the biomarker cf TTMV HPV in HPV-positive oropharynx and head and neck cancer; Mohemmed Nazir Khan, MD, and Scott Roof, MD, are the ENT faculty who have been leading this research focus.

For a complete list of Mount Sinai presentations, click here.

Eirini Papapetrou, MD, PhD, is

Co-organizer of a symposium—

“Human Pluripotent Stem Cell-derived Hematopoiesis”—to be held in conjunction with the International Society of Experimental Hematology meeting on August 17.

• See Flyer.
• For more information, contact Dr. Papapetrou.

Icahn Genomics Institute Seminar Series

Thursday, September 7, 11 am

Hess Seminar Room A

Darrell Irvine, PhD

Associate Director, Koch Institute for Integrative Cancer Research

Massachusetts Institute of Technology

“Engineering Immunity in Infectious Disease and Cancer”

Triparna Sen, PhD, is an invited speaker at the IASLC 2023 World Conference on Lung Cancer to be held September 9-12, 2023. Dr. Sen’s lab focuses on the biology of small-cell lung cancer (SCLC); she will present “Applying Emerging Biomarkers in SCLC.” 

Save the Date - TCI Community Outreach and Engagement Retreat

September 29, 10 am - 1:30 pm

Annenberg Building, 5-205

Also via Zoom

Register

Attendee Information

John Mascarenhas, MD, is co-chairing The Chemotherapy Foundation Symposium, which will take place November 8-10 in New York City. Use “Mascarehas” for free registration. 

New Fellows

The Division of Hematology and Medical Oncology welcomed first-year fellows in July.

Click here to see the roster.

Mentoring Future Cancer Researchers

The Tisch Cancer Institute (TCI) proudly partners with the Center in Excellence for Youth Education (CEYE) in support of programming for high school students whose backgrounds are underrepresented in medicine with the goals of increasing diversity and helping prepare the students for careers in science and health care.

One of the initiatives—the CEYE Bioinformatics Summer Program, co-led by Dan Hasson, PhD, and Deniz Demircioglu, PhD, with TCI’s Bioinformatics for Next Generation Sequencing Core (BiNGS)—recruited Maryam Ibrahim from Townsend Harris High School in Flushing, NY, in 2021. She is currently a sophomore at Hunter College, majoring in biology. At Mount Sinai, Maryam investigates pharmacological modulation of apoptosis in the Chipuk Laboratory in collaboration with the Harvard T.H. Chan School of Public Health. When asked about her experience at Mount Sinai, Maryam said, "This opportunity has helped me discover a passion I never knew I had! I learn more about the scientific process every day, and I love spending time in the lab and stimulating my mind."

Matthew Brown, PhD candidate at the Icahn School of Medicine at Mount Sinai, has received an Early Career Researcher Award from the Parker Institute for Cancer Therapy. Working in the Bhardwaj Laboratory, Matthew focuses on understanding antigen-specific T-cell responses and immune evasion in solid tumors with the goal or improving cancer vaccine design. Awardees are chosen from a highly competitive field on the basis of innovative research, scientific approach, the significance of the proposed work to advance cancer immunotherapy, and the promise of their research to accelerate the development of immune therapies for cancer.

More about Matthew Brown

The Icahn School of Medicine at Mount Sinai has joined the Caris Precision Oncology Alliance™ (POA), a network of 85 cancer centers, academic institutions, research consortia, and healthcare systems that collaborate to advance precision oncology and biomarker-driven research, and work together to optimize standards of care for molecular testing to improve clinical outcomes for cancer patients.

POA Members

The Mount Sinai Robert F. Smith Prostate Cancer Screening Mobile Unit has screened 3,000 patients since it launched in April 2022.

During the first eight months of operation, the mobile unit team saw more than 1,800 patients, 69 percent of whom were Black men. Of all those screened, between 15 and 18 percent had a PSA of 2.5 or above and were referred for follow-up care with a urologist.