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OA05.02 Anti-Tumor Immunity is a Key Determinant of SCLC Survivorship
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OA05.02 Anti-Tumor Immunity is a Key Determinant of SCLC Survivorship Farhad Kosari, Simone Terra, Aqsa Nasir, Prasuna Muppa, Marie Christine Aubry, Joanne Yi, Nafiseh Janaki, Aaron Mansfield, Mariza De Andrade, Ping Yang, George Vasmatzis, Virginia Van Keulen, Tobias Peikert Mayo Clinic, Rochester/United States of America Background: While the majority of small cell lung cancer (SCLC) patients succumb to their disease within a few months, there is a small group of patients who survive for many years after their diagnosis. Factors contributing to the SCLC long-term survivorship remain largely unknown. Herein, we compared tumors from exceptional survivors (EXS) and patients with the expected outcome (EOP) to determine genomic and immunological determinant of SCLC survivorship. Methods: In the Mayo Clinic tissue registry, we identified surgical blocks from 12 EXS who survived > 4 years after surgery and 14 EOP who died < 2 years of surgery. These cohorts were created to have no statistical differences in clinical TNM stage, curative versus non-curative intent surgery, age, gender, and smoking status between EXS and EOP. Tumor areas were macro-dissected for gene expression profiling by the Human Transcriptome Array (Affymetrix). Also, tissue sections were stained for key immunological markers, including CD8, CD4, CD3, CD279, FoxP3, CD138, CD20, CD21, CD14, CD68, and also LYZ. Concentrations of immune cells in intra-tumor areas (IE), stroma (ST), and tumor/non-tumor interface (IF) were assessed by an image processing program (Aperio). Staining patterns in each of the three zones in EXS and EOP tumors were compared. Results: More than 90% of differentially expressed genes were over-expressed in EXS compared with EOP. Furthermore, over 75% of the known over-expressed genes were either immunoglobulin or MHC related and a majority of the remaining genes were immune function related such as cytokines. We then performed IHC for key immunological markers and found significantly higher concentration of immune cells including CD8 and PD-1 positive cells in the tumor microenvironment, especially at the tumor stromal interface in EXS compared with EOP (p < 0.005 for both markers). Furthermore, the total number of infiltrating immune cells (T-cells, B-cells, Plasma cells, monocytes and macrophages was significantly higher in EXS in the interface region (p < 0.0005).
Journal of Thoracic Oncology
Vol. 12 No. 1S
Conclusion: Gene expression profiling revealed that anti-tumor immunity is an important factor for SCLC survival. Further studies by IHC suggested the presence of immune cells especially cytotoxic T-cells in the tumor microenvironment and particularly at the tumor-stromal interface to be major contributors to long term survivorship in SCLC. These findings suggest that immunotherapeutic strategies may be effective for patients with SCLC. Keywords: exceptional survivors, anti-tumor immunity, expression profiling, tumor microenvironment
OA05.03 Single-Agent Rovalpituzumab Tesirine, a Delta-Like Protein 3 (DLL3)-Targeted Antibody-Drug Conjugate (ADC), in Small-Cell Lung Cancer (SCLC) David Spigel,1 M Catherine Pietanza,2 Todd Bauer,1 Neal Ready,3 Daniel Morgensztern,4 Bonnie S. Glisson,5 Lauren Averett Byers,5 Melissa Johnson,1 Howard Burris,1 Francisco Robert,6 Tae Han,7 Sheila Bheddah,7 Noah Theiss,8 Sky Watson,8 Deepan Mathur,8 Bharathi Vennapusa,8 Donald Strickland,9 Hany Zayed,7 Scott Dylla,7 Stanford Peng,7 Ramaswamy Govindan,4 Charles Rudin10 1Sarah Cannon Research Institute/tennessee Oncology, Nashville/ TN/United States of America, 2Memorial Sloan Kettering Cancer Center, New York/NY/United States of America, 3 Duke University Medical Center, Durham/NC/United States of America, 4Washington University School of Medicine in St. Louis, St. Louis/MO/United States of America, 5The University of Texas MD Anderson Cancer Center, Houston/TX/United States of America, 6University of Alabama - Birmingham, Birmingham/AL/United States of America, 7Abbvie Stemcentrx Llc, South San Francisco/ CA/United States of America, 8Roche Diagnostics, Tucson/ AZ/United States of America, 9Tennessee Oncology, PLCC, Sarah Cannon Research Institute, Nashville/TN/United States of America, 10Medicine, Memorial Sloan Kettering Cancer Center, New York/NY/United States of America Background: SCLC is one of the most deadly malignancies. Rovalpituzumab tesirine (SC16LD6.5, Rova-T) is a first-in-class ADC directed against DLL3, a novel target identified in tumor initiating cells and expressed in over 80% of SCLC cases. Methods: Seventy-four patients with progressive SCLC after at least one previous systemic therapy were
OA05.02 Anti-Tumor Immunity is a Key Determinant of SCLC Survivorship Farhad Kosari, Simone Terra, Aqsa Nasir, Prasuna Muppa, Marie Christine Aubry, Joanne Yi, Nafiseh Janaki, Aaron Mansfield, Mariza De Andrade, Ping Yang, George Vasmatzis, Virginia Van Keulen, Tobias Peikert Mayo Clinic, Rochester/United States of America Background: While the majority of small cell lung cancer (SCLC) patients succumb to their disease within a few months, there is a small group of patients who survive for many years after their diagnosis. Factors contributing to the SCLC long-term survivorship remain largely unknown. Herein, we compared tumors from exceptional survivors (EXS) and patients with the expected outcome (EOP) to determine genomic and immunological determinant of SCLC survivorship. Methods: In the Mayo Clinic tissue registry, we identified surgical blocks from 12 EXS who survived > 4 years after surgery and 14 EOP who died < 2 years of surgery. These cohorts were created to have no statistical differences in clinical TNM stage, curative versus non-curative intent surgery, age, gender, and smoking status between EXS and EOP. Tumor areas were macro-dissected for gene expression profiling by the Human Transcriptome Array (Affymetrix). Also, tissue sections were stained for key immunological markers, including CD8, CD4, CD3, CD279, FoxP3, CD138, CD20, CD21, CD14, CD68, and also LYZ. Concentrations of immune cells in intra-tumor areas (IE), stroma (ST), and tumor/non-tumor interface (IF) were assessed by an image processing program (Aperio). Staining patterns in each of the three zones in EXS and EOP tumors were compared. Results: More than 90% of differentially expressed genes were over-expressed in EXS compared with EOP. Furthermore, over 75% of the known over-expressed genes were either immunoglobulin or MHC related and a majority of the remaining genes were immune function related such as cytokines. We then performed IHC for key immunological markers and found significantly higher concentration of immune cells including CD8 and PD-1 positive cells in the tumor microenvironment, especially at the tumor stromal interface in EXS compared with EOP (p < 0.005 for both markers). Furthermore, the total number of infiltrating immune cells (T-cells, B-cells, Plasma cells, monocytes and macrophages was significantly higher in EXS in the interface region (p < 0.0005).
Journal of Thoracic Oncology
Vol. 12 No. 1S
Conclusion: Gene expression profiling revealed that anti-tumor immunity is an important factor for SCLC survival. Further studies by IHC suggested the presence of immune cells especially cytotoxic T-cells in the tumor microenvironment and particularly at the tumor-stromal interface to be major contributors to long term survivorship in SCLC. These findings suggest that immunotherapeutic strategies may be effective for patients with SCLC. Keywords: exceptional survivors, anti-tumor immunity, expression profiling, tumor microenvironment
OA05.03 Single-Agent Rovalpituzumab Tesirine, a Delta-Like Protein 3 (DLL3)-Targeted Antibody-Drug Conjugate (ADC), in Small-Cell Lung Cancer (SCLC) David Spigel,1 M Catherine Pietanza,2 Todd Bauer,1 Neal Ready,3 Daniel Morgensztern,4 Bonnie S. Glisson,5 Lauren Averett Byers,5 Melissa Johnson,1 Howard Burris,1 Francisco Robert,6 Tae Han,7 Sheila Bheddah,7 Noah Theiss,8 Sky Watson,8 Deepan Mathur,8 Bharathi Vennapusa,8 Donald Strickland,9 Hany Zayed,7 Scott Dylla,7 Stanford Peng,7 Ramaswamy Govindan,4 Charles Rudin10 1Sarah Cannon Research Institute/tennessee Oncology, Nashville/ TN/United States of America, 2Memorial Sloan Kettering Cancer Center, New York/NY/United States of America, 3 Duke University Medical Center, Durham/NC/United States of America, 4Washington University School of Medicine in St. Louis, St. Louis/MO/United States of America, 5The University of Texas MD Anderson Cancer Center, Houston/TX/United States of America, 6University of Alabama - Birmingham, Birmingham/AL/United States of America, 7Abbvie Stemcentrx Llc, South San Francisco/ CA/United States of America, 8Roche Diagnostics, Tucson/ AZ/United States of America, 9Tennessee Oncology, PLCC, Sarah Cannon Research Institute, Nashville/TN/United States of America, 10Medicine, Memorial Sloan Kettering Cancer Center, New York/NY/United States of America Background: SCLC is one of the most deadly malignancies. Rovalpituzumab tesirine (SC16LD6.5, Rova-T) is a first-in-class ADC directed against DLL3, a novel target identified in tumor initiating cells and expressed in over 80% of SCLC cases. Methods: Seventy-four patients with progressive SCLC after at least one previous systemic therapy were