Although immunotherapy is effective for many patients with lung cancer, increasing evidence suggests the tumor microenvironment (TME) plays a significant role in treatment and resistance.
Four presenters will discuss findings highlighting the importance of the TME across a range of lung cancer settings during a WCLC oral abstract session, “Precision Immunotherapy via Modulation of the Tumor Microenvironment.” The session will begin at 14:45 CEST on Monday, August 8, in Lehar 1.
The session, which will be moderated by Kurt Alex Schalper, MD, PhD, assistant professor of pathology and medicine at Yale University, and Umberto Malapelle, PhD, a researcher in anatomic pathology in the Department of Public Health at the University of Naples, will be followed by a question-and-answer discussion.
Precision Immunotherapy via Modulation of the Tumor Microenvironment
- Time: 14:45-15:45 CEST
- Date: Monday, August 8
- Location: Lehar 1
“The TME plays a critical role in both cancer progression and treatment resistance. In addition, data suggest that transforming the TME to an immunomodulatory state may have a major influence on cancer outcomes,” Dr. Malapelle said. “Thus, increasing our knowledge about the TME is required so that we can better understand tumor development and evolution and plan the best treatment options for patients with cancer.”
Exploring the Findings
Dr. Malapelle offered previews of the talks that will be given during the session. First, Tao Wang, PhD, Vice President of Research and Development at Hangzhou Repugene Technology Co. Ltd., China, will present “Single Cell Analyses Reveal Effects of Immunosenescence Cells in Neoadjuvant Immunotherapy of Lung Squamous Cell Carcinoma Patients.”
As many patients with lung cancer are older, immunosenescence—a type of immune dysfunction resulting from age-related pro-inflammatory stimulation—can affect their treatment outcomes. In patients with squamous cell carcinoma of the lung, this study confirms a correlation between immunosenescent cells and poor responses to neoadjuvant immunotherapy, Dr. Malapelle said.
Next, Shruti Desai, PhD, who is an associate research scientist in the Department of Pathology at Yale University, New Haven, Connecticut, will present “Spatial Mapping and Clinical Significance of the LAG-3/FGL1 Pathway in Non-small Cell Lung Cancer Using High-Dimensional Tissue Imaging.”
This study highlights the promise of the LAG3/FGL-1 axis as a biomarker that could serve as a target for new lung cancer immunotherapies, Dr. Malapelle said.
“The study found that high expression of the immune inhibitory T-cell receptor LAG3 and its ligand, FGL1, boosts tumor growth by inhibiting the immune microenvironment,” he said. “That, in turn, interferes with the success of PD-1 blockade.”
Jonathan Villena-Vargas, assistant professor at Weill Cornell Medicine, New York, will then present “Neoadjuvant IL-15-PDL1 Antibody Promotes T-cell Memory and Decreases Metastatic Recurrence in Resectable NSCLC.”
Within the tumor draining lymph nodes, the cytokine IL-15 promotes CD8-positive T-cell and natural killer cell activation, proliferation, cytotoxicity, and survival. “For this reason, the adoption of IL-15 superagonists may play a synergistic role with anti-PD-L1 antibodies, improving long-term patient outcomes,” Dr. Malapelle said.
Finally, Emmanuel Nwadozi, PhD, of Uppsala University, will present “Vascular Leakage Promotes Immunosuppression and is Associated with Reduced Patient Survival in Non-Small Cell Lung Cancer.”
“Lymphatic vascular leakage promotes an immunosuppressive TME by enhancing anti-inflammatory macrophage differentiation. Because this process reduces patient survival, it will continue to constitute an important research focus,” Dr. Malapelle said.
Further Investigation is Needed
Dr. Malapelle hopes the studies presented during the session will inspire many future investigations of the TME in lung cancer.
“Careful attention must be paid to this area of research,” he said. “Several studies have evaluated the main aspects of immunotherapy administration. Now, further studies are needed to better explain all the aspects that may influence responsiveness to these drugs.”