Nav: Home

Hybrid immune cells in early-stage lung cancer spur anti-tumor T cells to action

July 14, 2016

PHILADELPHIA - The microenvironment of tumors is a mix of cell types, mostly comprised of inflammatory cells. White blood cells, recruited from the blood and bone marrow, represent a significant portion of these inflammatory cells and influence nearly all steps of tumor progression. One type, called tumor associated neutrophils (TANs), predominates; however, the role of TANs in tumor development remains largely unexplored in humans.

Researchers from the Perelman School of Medicine at the University of Pennsylvania have now identified a unique subset of these cells that exhibit hybrid characteristics of two immune cell types -- neutrophils and antigen-presenting cells -- in samples from early-stage human lung cancers. This is the first study to describe this phenomenon in a human tumor. Senior author Evgeniy B. Eruslanov, PhD, a research assistant professor from the Department of Surgery, and colleagues published their findings this month in Cancer Cell.

The goal of this research was to characterize TANs and determine their specific roles in the regulation of T cell responses in patients with early-stage lung cancer. Understanding the role of TANs in regulating T cell responses in cancer patients is particularly important because cytotoxic T lymphocytes are the chief effector cells mediating antitumor immunity.

"We tried to ascertain the function of this hybrid subset of TANs," Eruslanov said. "Are they there to help the tumor grow or to fight its existence? We show that small size, early-stage lung tumors can induce the formation of a unique type of tumor-associated cells that can trigger and support anti-tumor T cell responses, thus potentially limiting the growth of the cancer" Eruslanov said.

To figure out how to harness natural anti-tumor capabilities of immune cells, they needed to know what happens in human tumor tissue. This was made possible by coauthor Sunil Singhal, MD, an associate professor of Surgery, who provided fresh tumor tissue from lung-cancer patients and participated in research.

"Our findings demonstrate that the early-stage lung tumor microenvironment can drive neutrophils to differentiate into a cell subset with enhanced anti-tumor capabilities. Interestingly, this hybrid population disappears as tumors enlarge," Singhal said.

These findings demonstrate the potential anti-tumor role of these cells in early-stage cancer and may provide opportunities to boost the anti-tumor efficacy of cytotoxic T cells. An understanding of the cellular and molecular processes in early stage tumors will allow researchers to identify which immune forces need to be augmented to facilitate natural protection against tumor development.

"We want to take advantage of these unique early tumor neutrophils to help them better stimulate the anti-tumor cytotoxic T cells," Eruslanov said. "Perhaps if we can expand the hybrid neutrophils in patients early on, we can augment anti-tumor T cell activity."
-end-
Other coauthors are Pratik S. Bhojnagarwala, Shaun O'Brien, Edmund K Moon, Alfred L. Garfall, Abhishek Rao, Jon G. Quatromoni, Tom Li Stephen, Leslie Litzky, Charuhas Deshpande, Michael Feldman, Wayne W. Hancock, Jose R Conejo-Garcia, and Steven M. Albelda, all from Penn.

This research was supported by the Department of Defense (LC140199), the National Cancer Institute (RO1 CA187392-01A1, RO1 CA193556, K12CA076931), and the Lung Cancer Translation Center of Excellence of the Abramson Cancer Center at Penn.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $5.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 18 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $373 million awarded in the 2015 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2015, Penn Medicine provided $253.3 million to benefit our community.

University of Pennsylvania School of Medicine

Related Cancer Articles:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Related Cancer Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#529 Do You Really Want to Find Out Who's Your Daddy?
At least some of you by now have probably spit into a tube and mailed it off to find out who your closest relatives are, where you might be from, and what terrible diseases might await you. But what exactly did you find out? And what did you give away? In this live panel at Awesome Con we bring in science writer Tina Saey to talk about all her DNA testing, and bioethicist Debra Mathews, to determine whether Tina should have done it at all. Related links: What FamilyTreeDNA sharing genetic data with police means for you Crime solvers embraced...