Article Text

Download PDFPDF

Multispectral imaging and objective assessment of immune-tumor interactions in non-small cell lung cancer
  1. Carmen Ballesteros-Merino1,
  2. Michael Neuberger2,
  3. Zipei Feng1,
  4. Rudolf Maria Huber3,
  5. Julia Stump3,
  6. Amanda Tufman3,
  7. Rudolf Hatz2,
  8. Michael Linder4,
  9. Rachel Sanborn1,
  10. Sanaa Hussain1,
  11. John R Handy1,
  12. Walter Urba5,
  13. Bernard Fox5,
  14. Carlo Bifulco6,
  15. Simone Reu7 and
  16. Hauke Winter2
  1. Aff1 grid.415286.c0000 0004 0463 5556Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer Center Portland Oregon USA
  2. Aff2 grid.411095.80000 0004 0477 2585Department of General, Visceral, Transplantation, Vascular and Thoracic SurgeryHospital of the Ludwig Maximilian University, Munich, Germany Comprehensive Pneumology Center (CPC) and Member of the German Center for Lung Research Munich Germany
  3. Aff3 grid.5252.0000000041936973XComprehensive Pneumology Center (CPC) and Member of the German Center for Lung Research, Munich, Germany Division of Respiratory Medicine and Thoracic Oncology, Department of Internal Medicine VThoracic Oncology Centre LMU Munich Munich Germany
  4. Aff4 Comprehensive Pneumology Center (CPC) and Member of the German Center for Lung Research, Munich, GermanyAsklepios Clinic Munich-Gauting Munich, Munich Germany, Germany
  5. Aff5 grid.415286.c0000 0004 0463 5556Earle A. Chiles Research Institute Portland OR USA
  6. Aff6 grid.415286.c0000 0004 0463 5556Earle A. Chiles Research Institute, Providence Cancer Center Portland OR USA
  7. Aff7 Comprehensive Pneumology Center (CPC) and Member of the German Center for Lung Research, Munich, GermanyInstitute of Pathology, University of Munich Munich, Munich Germany, Germany

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Meeting abstracts

Lung cancer is currently the most common cause of cancer-related death in the world and approximately 85% of all lung cancers are non-small cell lung cancer (NSCLC). Previous studies have shown that patients with NSCLC containing high densities of CD8+ memory T cells have a survival advantage. Others have identified an association between relatively high numbers of regulatory T cells and poor prognosis. Our group is interested in better characterizing the immune infiltrates and refining prognostic biomarkers that identify patients at risk of recurrence. Recent advances in multispectral imaging provide an opportunity to evaluate up to 7 markers in a single 4 micron section of formalin-fixed paraffin-embedded (FFPE) tissue. Using this technology, we reported that a high ratio of CD8:FoxP3 at the tumor correlated with the ability to isolate tumor-specific T cells from melanomas (Feng et al., submitted). This determination could be further improved by incorporating the ratio of CD8:PD-L1 present in the tumor into the evaluation. Now we are applying these same strategies to the study of NSCLC. Initial analyses have been performed on more than 450 tumor cores from 77 patients with Stage 3A/3B/4 NSCLC and included the following markers: CD3, CD8, FoxP3, CD163 and PD-L1. Additional markers are being evaluated. Ultimately, we expect that this approach could be used to stratify patients for clinical trials. We anticipate that some biomarkers will identify suppressive pathways and be associated with a short progression-free survival. While we expect there will be heterogeneity in escape mechanisms, identification of a specific mechanism could be used to tailor therapy with an agent or agents to overcome the specific immune suppressive pathway operational in that specific tumor. Patients who lack evidence for a specific suppressive pathway would be randomized to treatment with combination immunotherapy that includes a cancer vaccine.

Footnotes

  • Author's Contribution Drs. Ballesteros-Merino and Neuberger; and Drs. Reu and Winter contributed equally to this work. Supported by the Harder Family, Lynn and Jack Loacker, Robert W. Franz, Wes and Nancy Lematta, Providence Medical Foundation.