Publication date: 4 April 2017
Source:Cell Reports, Volume 19, Issue 1
Author(s): Takahiro Tsujikawa, Sushil Kumar, Rohan N. Borkar, Vahid Azimi, Guillaume Thibault, Young Hwan Chang, Ariel Balter, Rie Kawashima, Gina Choe, David Sauer, Edward El Rassi, Daniel R. Clayburgh, Molly F. Kulesz-Martin, Eric R. Lutz, Lei Zheng, Elizabeth M. Jaffee, Patrick Leyshock, Adam A. Margolin, Motomi Mori, Joe W. Gray, Paul W. Flint, Lisa M. Coussens
Here, we describe a multiplexed immunohistochemical platform with computational image processing workflows, including image cytometry, enabling simultaneous evaluation of 12 biomarkers in one formalin-fixed paraffin-embedded tissue section. To validate this platform, we used tissue microarrays containing 38 archival head and neck squamous cell carcinomas and revealed differential immune profiles based on lymphoid and myeloid cell densities, correlating with human papilloma virus status and prognosis. Based on these results, we investigated 24 pancreatic ductal adenocarcinomas from patients who received neoadjuvant GVAX vaccination and revealed that response to therapy correlated with degree of mono-myelocytic cell density and percentages of CD8+ T cells expressing T cell exhaustion markers. These data highlight the utility of in situ immune monitoring for patient stratification and provide digital image processing pipelines to the community for examining immune complexity in precious tissue sections, where phenotype and tissue architecture are preserved to improve biomarker discovery and assessment.
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Tsujikawa et al. develop a multiplex immunohistochemistry and image cytometry platform to reveal immune-based metrics for patient stratification and response monitoring. In HNSCC and PDAC, prognosis correlates with mono-myelocytic cell density. In PDAC, percentages of PD-1, Eomes, Ki67, and granzyme B in CD8+ T cells correlate with response to vaccine therapy.http://ift.tt/2nJSNow
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