Roswell Park Teams Report Latest Findings on Obesity & Cancer, Other High-Priority Research at AACR 2024

BUFFALO, N.Y. — Researchers from Roswell Park Comprehensive Cancer Center will share their latest findings with colleagues from around the world at the 2024 annual meeting of the American Association for Cancer Research (AACR) in San Diego, California, April 5-10. The event attracts more than 21,000 professionals from the oncology field, as well as patients, survivors and advocates.

Major Symposium 

Obesity is now recognized as a leading cause of cancer, second only to smoking. The work of Roswell Park faculty will be featured in two presentations addressing that issue during a major symposium on The Growing Impact of Obesity on Cancer and Cancer Immunotherapy Outcomes, Monday, April 8, from 10:15-11:45 a.m. PDT in the San Diego Conference Center, Room 30, upper level:

• Sai Yendamuri, MD, MBA, FACS, Chair of Thoracic Surgery, will discuss his team’s identification of two “confounding factors” that contradict the results of previous studies that found overweight and obesity to be beneficial for lung cancer patients. Those factors include the widespread use of body mass index (BMI) — a deeply flawed measure — to define obesity, and the fact that many commonly prescribed medications have a secondary anticancer effect in obese patients but not nonobese patients. In both preclinical and clinical studies, the team also revealed that obesity’s effects on the immune response enable lung cancer cells to proliferate. These findings have implications for improving the design of future studies to more accurately gauge the effects of obesity in cancer patients. Led by Dr. Yendamuri, the study was co-authored by Santosh Patnaik, MD, PhD, Assistant Professor of Oncology, Department of Thoracic Surgery, and Joseph Barbi, PhD, Assistant Professor of Oncology, Department of Immunology at Roswell Park. The work will be presented during Session SY38-02, “Clinical investigations of obesity in cancer: BMI and other confounders,” on Monday, April 8, 10:45-11:05 a.m.
• Spencer Rosario, PhD, Assistant Member, Department of Biostatistics and Bioinformatics, and Director of the Bioanalytics, Metabolomics & Pharmacokinetics Shared Resource, is co-author of a study to be presented as part of the same symposium — Session SY39-01, “Diverse effects of obesity on cancer immunology and therapy: Both the good and the bad,” Monday, April 8, 10:20-10:40 a.m. PDT. Dr. Rosario also contributed both metabolomics research and an understanding of immunometabolism to the symposium’s introduction, to help frame the way obesity should be considered in terms of the crosstalk between immunology and metabolism.
  
  

Featured Posters Highlight Other Roswell Park-Led Research

During the meeting, Roswell Park research teams will present posters documenting several other Roswell Park-led efforts advancing understanding in key areas of oncology:

• First author Aftab Alam, PhD, postdoctoral Research Affiliate, Department of Immunology, will present Fungi utilizes exocytosis pathway to facilitate the release of DAMPs from pancreatic cancer cells (Abstract 6674/5). The study identifies a new treatment target, EXOC6B, a gene involved in the secretion of interleukin 33, which promotes treatment resistance in pancreatic cancer. Prasenjit Dey, PhD, Associate Professor of Oncology, Department of Immunology, is senior author of the study. Dr. Alam also has been recognized for this meritorious abstract with a 2024 AACR Scholar-in-Training Award supported by an independent educational grant from AbbVie.
• Mohammed Muharrab Alruwaili, MS, ASCP, predoctoral trainee in Cancer Genetics & Genomics, will describe a novel therapeutic strategy for selective targeting of p53-mutant colorectal cancers by affecting post-replicative DNA repair — a strategy that may provide an effective treatment option for aggressive p53-mutant colorectal cancers — in Novel therapeutic approach for targeting p53 mutant colorectal cancers by affecting post-replicative DNA repair (Abstract 7590/17), for which he is first author. Andrei Bakin, PhD, Associate Professor of Oncology, Department of Cancer Genetics and Genomics, is senior author of the study. 
• Rikki Cannioto, PhD, EdD, MS, Assistant Professor of Oncology, Department of Cancer Prevention and Control, is first author of a study evaluating the use of waitlist control in exercise oncology and will discuss the results, in The impact of a waitlist control group on physical activity level in the Activity after Cancer Treatment exercise oncology randomized pilot study (Abstract 2246/20). Christine Ambrosone, PhD, Senior Vice President for Population Sciences and Chair of Cancer Prevention and Control at Roswell Park, is senior author of the study. 
  • Dr. Cannioto will also present the results of a study showing that CD8+ T-cell density, which is associated with better survival outcomes, was significantly higher in breast cancer patients who met the Physical Activity Guidelines compared with those who were inactive. Dr. Cannioto is first author and Dr. Ambrosone is senior author of the study, entitled Meeting the Physical Activity Guidelines is associated with increased CD8+ T-cell density in the tumor microenvironment of breast cancer patients (Abstract 5403/21). 
  • Dr. Cannioto will report the results of a study showing that obesity is linked to higher mortality in patients who have the most aggressive type of ovarian cancer, in Disentangling the obesity paradox in high-grade serous epithelial ovarian cancer (Abstract 3403/5). Dr. Cannioto is senior author and Evan W. Davis, MPH, predoctoral trainee in the Department of Cancer Prevention and Control, is first author of the study.
• First author Jee Eun Choi, predoctoral trainee in Immunology, will present Understanding the role of β2-adrenergic receptor signaling on type II innate lymphoid cells in cancer, describing how increased norepinephrine due to chronic stress promotes an immunosuppressive tumor environment (Abstract 105/9). Elizabeth Repasky, PhD, Vice Chair of Immunology and Co-Leader of the Cancer Stress Biology Program at Roswell Park, is senior author. 
• Bowen Dong, predoctoral trainee in Immunology, is first author and Pawel Kalinski, MD, PhD, Chair of Immunology, is senior author on NK receptors enable TCR-mediated CTL recognition and killing of cancer cells expressing non-mutated tumor-associated antigens (Abstract 3966/8).
• Peter Fiorica, predoctoral trainee in Cancer Prevention & Control, is first author and Song Yao, MD, PhD, is senior author on Mendelian randomization analysis of 27 cardiometabolic trait related polygenic scores identifies genetic risk for cardiometabolic and cardiovascular events in a large prospective study of breast cancer survivors (Abstract 3462/17).
• First author Opuruiche Ibekwe, MBBS, MPH, DrPH, Research Associate, Department of Thoracic Surgery, will compare the before-and-after impact of adopting Navify tumor board solution technology on the quality of information presented, case discussion and care plans at thoracic multidisciplinary cancer conferences. Chukwumere Nwogu, MD, PhD, FACS, Professor of Oncology and Attending Surgeon in Thoracic Surgery, is senior author of the study, Impact of technology on quality of thoracic multidisciplinary cancer conferences (Abstract 4973/9).
• Renuka Iyer, MD, Co-Leader of the Liver and Pancreas Tumor Program and Chief of Gastrointestinal Oncology, is first and presenting author of the results of a clinical trial, Phase Ib/II study of sorafenib (SOR) and pembrolizumab (PEM) in patients (pts) with advanced hepatocellular carcinoma (HCC). Christos Fountzilas, MD, FACP, Co-Leader of the Gastrointestinal Clinical Disease Team and Associate Director for Solid Tumors, Early Phase Clinical Trials Program at Roswell Park, is senior author. This marks the first presentation of the study results.
• Sheheryar Kabraji, BMBCh, Associate Professor of Oncology and Director of Breast Translational Research, is first author on Residual disease after HER2 inhibition is driven by a primary tumor subpopulation expressing an ERBB2-low associated transcriptional program (Abstract 6939/17).
• First author Shyamananda Singh Mayengbam, PhD, postdoctoral Research Affiliate, Department of Immunology, will share his team’s findings that obesity-driven pancreatic ductal adenocarcinoma is regulated through increased intratumoral nerve innervation and can be targeted by blocking adrenergic signals, in Obesity-mediated perineural invasion promotes PDAC tumorigenesis (Abstract 6818/23), a study for which Dr. Dey is senior author. Dr. Mayengbam also has been recognized with a 2024 AACR-Doreen J. Putrah Cancer Research Foundation Scholar-in-Training Award, funded by the Doreen J. Putrah Cancer Research Foundation. 
• James Mohler, MD, Chair Emeritus of Urology, is senior author on Associations between plant- and animal-based dietary patterns and aggressive prostate cancer in the North Carolina-Louisiana prostate cancer project (PCaP) (Abstract 2172/6).
• Daniel Alvarado, formerly of the Department of Medicine, is first author and Michael Nemeth, PhD, of the Department of Immunology, Co-Chair of Leukemia Translational Research, is senior author on Activating anti-MDS immunity with polarized dendritic cell vaccines (Abstract 6744/13).
• First author Priyanka Rajan, predoctoral trainee, Cancer Genetics & Genomics, will discuss a study showing that blockade of p38 MAP kinase reduces the immune-suppressive microenvironment in metastatic breast cancer. Her presentation is The role of p38 MAPK in the tumor-induced immune suppressive microenvironment in metastatic breast cancer (Abstract 5536/25), for which Dr. Bakin is senior author. 
• Sora Suzuki, predoctoral trainee in Immunology, is first author and presenter on two poster abstracts: He worked with senior author Brahm Segal, MD, Chair of Internal Medicine, Chief of Infectious Diseases, on Targeting complement factor H renders STK11-mutant lung adenocarcinoma sensitive to anti-PD-1 therapy in mice (Abstract 2915/23). He worked with senior author Edwin Yau, MD, PhD, Assistant Professor of Oncology, Departments of Medicine and Cancer Genetics & Genomics, on Tumor-derived complement C3 is overexpressed in STK11 mutant non-small cell lung cancer and contributes to an immunosuppressive tumor microenvironment in a syngeneic mouse model (Abstract 108/12) — a preclinical study showing that a combination of single-agent Cxcr2 inhibitor and anti-PD-1 therapy resulted in significant suppression of tumor growth in non-squamous non-small cell lung cancer.
• Kazuaki Takabe, MD, PhD, FACS, FSSO, Chair of Breast Surgery, is senior author on six poster abstracts:
  • Enhancing immune checkpoint inhibitor efficacy with fulvestrant in estrogen receptor-positive breast cancer (Abstract 7515/3), to be presented by first author Jun Arima MD, PhD, a postdoctoral researcher in Surgical Oncology.
  • Gastric cancer with high neuron infiltration was associated with enhanced epithelial-to-mesenchymal transition, angiogenesis and poor clinical outcomes (Abstract 2570/30), to be presented by first author Kohei Chida, MD, Research Affiliate in Surgical Oncology.
  • High infiltration of neurons was associated with lower cell proliferation and less immune response but not with response to treatments or survival in estrogen receptor-positive breast cancer (Abstract 2568/28), which will also be presented by Dr. Chida, first author.
  • CD133 expression is associated with less DNA repair, better response to chemotherapy, and survival in ER-positive/ER-negative breast cancer (Abstract 2520/8), to be presented by first author Takumi Sato, MD, who previously trained at Roswell Park.
  • VEGFA gene expression is associated with cell proliferation, less immune cell infiltration, and worse survival, but better response to chemotherapy and immunotherapy (Abstract 2569/29), to be presented by first author Pia Sharma, a Research Assistant in Surgical Oncology.
  • Activity-regulated cytoskeleton-associated protein (ARC) gene expression is associated with high infiltration of stromal cells and immune cells, but with less cancer cell proliferation and better overall survival in ER-positive/HER2-negative breast cancer (Abstract 2549/9), to be presented by first author Gabrielle Yee, MD, a resident physician in general surgery who completed a rotation in Surgical Oncology. 
• Deepak Vadehra, DO, Assistant Professor of Oncology and Co-Leader of the Adolescent/Young Adult (AYA) Translational Research Group in Roswell Park’s Department of Medicine, is first author of a study that used the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database to characterize the incidence of secondary malignancies in patients with early-onset colorectal cancer. He will report the results of Incidence of secondary malignancies in early-onset colorectal cancer (EOCRC) patients (Abstract 7449/11), for which Sarbajit Mukherjee, MD, MS, Co-Leader of the GI Translational Research Group at Roswell Park, is senior author. 
• Dr. Vadehra will also present a synopsis of a clinical trial in progress, in A phase 0 study of EGF-depleting therapy CIMAvax-EGF in combination with standard therapy for RAS- and BRAF wild-type metastatic colorectal cancer (Abstract CT126/5). Dr. Vadehra is first author and study principal investigator on the abstract, and Dr. Fountzilas is senior author.

The investigators gratefully acknowledge support from both public and private funding organizations, including the Roswell Park Alliance Foundation, the Breast Cancer Research Foundation and numerous National Institutes of Health agencies, in making this work possible. 

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From the world’s first chemotherapy research to the PSA prostate cancer biomarker, Roswell Park Comprehensive Cancer Center generates innovations that shape how cancer is detected, treated and prevented worldwide. Driven to eliminate cancer’s grip on humanity, the Roswell Park team of 4,000 makes compassionate, patient-centered cancer care and services accessible across New York State and beyond. Founded in 1898, Roswell Park was among the first three cancer centers nationwide to become a National Cancer Institute-designated comprehensive cancer center and is the only one to hold this designation in Upstate New York. To learn more about Roswell Park Comprehensive Cancer Center and the Roswell Park Care Network, visit www.roswellpark.org, call 1-800-ROSWELL (1-800-767-9355) or email ASKRoswell@RoswellPark.org.