Abstract 595: Heterogeneity of immune checkpoint expression in lung cancer identified through rapid tissue donation
Authors: Boyle Theresa , Shaffer Andrea , Hudson Janella N. , Arevalo Luisa D. , Schabath Matthew , Muñoz-Antonia Teresita , Pratt Christie , Quinn Gwendolyn P. , Haura Eric B. 
Published: July 2017

Background: Translational research in advanced lung cancer is hindered by the limited availability of specimens for advanced molecular techniques. Although helpful, the standard practice to biopsy a small amount of tissue from a single site of cancer provides limited information. We launched a thoracic rapid tissue donation (RTD) program to enable lung cancer research with collection of tissue at multiple tumor sites within hours after death. Many patients chose to enroll in the RTD program as an opportunity to contribute to cancer research. RTD tissue will support multiple research projects, such as studying differential expression of immune checkpoint proteins in immune oncology or understanding resistance to targeted agents.

Methods: The RTD program for patients with stage IV lung cancer was approved in June 2015 by the Moffitt Cancer Center institutional review board. Tissue specimens from multiple tumor sites from consented donors are collected rapidly (aim &lt; 24 hours) after death and are frozen and/or preserved in formalin. Hematoxylin and eosin (H&E) staining is performed with evaluation of the histopathology and quality of the specimens. Immunohistochemistry is performed to evaluate expression of immune checkpoint biomarkers (PD-L1, CTLA4, LAG3, TIM3, BTLA, A2aR and iNOS).

Results: Between June 26, 2015 and November 16, 2016, 18 patients with stage IV lung cancer consented to the RTD program. Post-mortem tissue has been collected from multiple tumor sites for three cases. H&E staining of 25 tissue blocks from the first case showed minimal evidence of post-mortem tissue damage by autolysis, confirming high RTD tissue quality. Biomarker studies, such as immunohistochemistry for immune checkpoints, such as PD-L1, CTLA4, LAG3, TIM3, BTLA, A2aR and iNOS are ongoing. Preliminary analysis of PD-L1 expression in the first patient revealed heterogeneous PD-L1 expression within and between eight tumor sites (both lungs, liver, both kidneys, left adrenal gland, mediastinal and retroperitoneal lymph nodes).

Conclusions: Rapid tissue donation with collection of ample post-mortem tumor tissue is feasible and valuable for cancer research. A heterogeneous pattern of PD-L1 immune checkpoint expression was observed between multiple sites of tumor. Post-mortem tissue collection from multiple tumor sites facilitates understanding changes in tumor behavior and biomarker expression at metastatic sites, especially in the context of treatment failures.

Acknowledgements: NIH Sponsor #R21 CA194932-01 and Tissue Core Facility at the H. Lee Moffitt Cancer Center & Research Institute (P30-CA076292).

Citation Format: Theresa Boyle, Andrea Shaffer, Janella N. Hudson, Luisa D. Arevalo, Matthew Schabath, Teresita Muñoz-Antonia, Christie Pratt, Gwendolyn P. Quinn, Eric B. Haura. Heterogeneity of immune checkpoint expression in lung cancer identified through rapid tissue donation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 595. doi:10.1158/1538-7445.AM2017-595