Untersuchung der Immunmodulation und Korrelation mit dem Ansprechen auf eine neo-adjuvante Immuntherapie bei Lungenkarzinompatienten in frühem Tumorstadium
Pneumologie,Thoraxchirurgie
Zusammenfassung der Projektergebnisse
To date, is has not been fully understood how the immune system is modulated in non-small cell lung cancer patients treated with immunotherapy and how this is correlated with response, progression and the development of immune-related adverse events (irAEs). We have conducted comprehensive immunophenotyping in lymph node and peripheral blood samples of 179 out of planned 180 early stage NSCLC patients treated with the anti-PD-L1 agent atezolizumab in the LCMC3 trial. To date, we have collected and analyzed 179 pre- and posttreatment peripheral blood samples, 54 screening lymph node samples and 77 surgical lymph node samples from 16 sites in the United States. The enrollment has been nearly completed. Data cleaning for final analysis will take another couple of months, however the preliminary results, which have been presented orally at three international conferences are very promising. We could, as initially proposed, show the feasibility of comprehensive flow-cytometry (10-color, 14-tube, 60-marker IMMUNOME and TCR Vβ)- based immunophenotyping using endobronchial ultrasound-guided transbronchial needle aspirates from lymph nodes. In surgical lymph nodes, immunosuppressive/regulatory T cell subsets were less abundant in patients who achieved MPR compared to those who did not. Other T cell subsets which support the anti-tumor immune response showed higher abundances in patients who achieved MPR. In the peripheral blood, immunosuppressive T cell subsets were more abundant in non-major pathological responders and progressors and unspecific immunoprotective cell subsets showed higher abundances in patients who developed irAEs. Our collaborators analyzed tumor mutational burden in 50 primary tumor screening samples and did not observe a correlation with pathological regression or MPR. Analysis of the full data set of 180 patients including flow cytometry, cytokine bead arrays, TCR immunosequencing and others will further our understanding on MPR-specific immunophenotypes in peripheral blood and lymph nodes as well as immunophenotypes specific for the occurrence of immune-related adverse events. We will be analyzing all samples at baseline and at surgery and will the aim to discover predictive biomarkers.
Projektbezogene Publikationen (Auswahl)
- World Conference on Lung Cancer (WCLC), Toronto, Canada 2018. Comprehensive peripheral blood immunophenotyping and T-cell clonal analysis during neoadjuvant immunotherapy with atezolizumab in NSCLC
Filiz Oezkan, Kai He, Dwight Owen, Maciej Pietrzak, Rhonda Kitzler, Rebecca Pearson, Alan Nicholas, Paul Bunn, Mark Kris, David J. Kwiatkowski, Bruce E. Johnson, Fred R. Hirsch, Ignacio Wistuba, Valerie Rusch, Jay M. Lee, Mayank Gandhi, Katja Schulze, David S. Shames, Gerard Lozanski, David P. Carbone
(Siehe online unter https://doi.org/10.1016/j.jtho.2018.08.347) - ASCO-SITC Clinical Immuno-Oncology Symposium, San Francisco, US 2019. Neoadjuvant atezolizumab in resectable NSCLC patients: updated clinical and Immunophenotyping results from a multicenter trial
Filiz Oezkan, Kai He, Dwight Hall Owen, Maciej Pietrzak, Valerie W. Rusch, Jamie E. Chaft, Rhonda Kitzler, Alan Nicholas, Katja Schulze, Ann Johnson, See Phan, Paul A. Bunn Jr., Mark G. Kris, David J. Kwiatkowski, Bruce E. Johnson, Ignacio Ivan Wistuba, Jay M. Lee, Fred R. Hirsch, Gerard Lozanski, David Paul Carbone
(Siehe online unter https://doi.org/10.1200/JCO.2019.37.8_suppl.99) - World Conference on Lung Cancer (WCLC), Barcelona, Spain 2019. Neoadjuvant atezolizumab in resectable NSCLC patients: Clinical and Immunophenotyping results from the interim analysis of the multicenter trial LCMC3
Filiz Oezkan, Kai He, Dwight H. Owen, Maciej Pietrzak, Ju Hwan Cho, Rhonda Kitzler, Rebecca Pearson, Valerie W. Rusch, Jamie E. Chaft, Robert Suh, Justin D. Blasberg, Karen L. Reckamp, Dan J. Raz, Peter J. Kneuertz, Lauren Fiorillo, Edward Garon, Alan Nicholas, Ann Johnson, Katja Schulze, See Phan, Paul A. Bunn Jr., David J. Kwiatkowski, Bruce E. Johnson, Mark G. Kris, Ignacio Ivan Wistuba, Jay M. Lee, Gerard Lozanski, David P. Carbone
(Siehe online unter https://doi.org/10.1016/j.jtho.2019.08.482)
