Abstract P3-09-17: Preoperative pembrolizumab increases sTILs in treatment naïve stage I/IIA TNBC patients in a window of opportunity trial

Autor: Rami Vanguri, Tahsin Kurc, Joel H. Saltz, Rajarsi Gupta, Dimitris Samaras, Shahira Abousamra, Kevin Gardner, Han Le, Hua Guo, Kevin Kalinsky, Shuobo Boboila, Le Hou, Hanina Hibshoosh, Eileen P. Connolly
Rok vydání: 2020
Předmět:
Zdroj: Cancer Research. 80:P3-09
ISSN: 1538-7445
0008-5472
Popis: Background: High levels of stromal tumor-infiltrating lymphocytes (sTILs) are significantly associated with chemosensitivity and improved overall survival for patients with triple negative breast cancer (TNBC). Our aim is to determine if we can significantly increase sTILs from biopsy to lumpectomy in a presurgical window of opportunity trial with pembrolizumab and intraoperaperative radiation (IORT) in treatment-naïve early stage TNBC compared to matched IORT only controls. We also evaluate the changes in the spatial distribution of intraepithelial TILs (iTILs) by utilizing a deep learning algorithm. Our secondary aim is to characterize the tumor immune microenvironment (TME) using quantitative multiplex immunofluorescence (qmIF) and transcriptomic analysis of tumor-associated and immune genes. Methods: Seven women with node negative TNBC Results: Seven patients were enrolled between Nov 2017-Apr 2019; 3 patients received pembrolizumab+IORT; and 4 patients received IORT alone. Initial pathology assessment of sTILs demonstrated no significant change between biopsy and lumpectomy in control patients. No consistent patterns of iTILs dispersion were observed in the control patients. Out of the 3 pembrolizumab treated patients, one patient demonstrated a marked increase in sTILs (20% to 60%) with a shift from a neutrophil rich to lymphoplasmacytic stromal infiltrate where the mean dispersion of the iTILs doubled (180 to 360). In the other 2 pembrolizumab patients, one remained stable and one showed a slight increase in sTILs. The iTILs dispersion increased significantly in these patients (from 40 to 90 and 10 to 280, respectively). A corresponding spatial analysis of sTILs is ongoing. Additionally, qmIF and transcriptomic analysis of tumor-associated and immune genes is currently underway to compare biopsy and surgical specimens. Conclusion: In this preliminary analysis, we observe preoperative pembrolizumab-induced increases in sTILs with increased mean dispersion of iTILs in treatment naïve TNBC. Our initial analysis in this ongoing trial appears promising after examining changes in both the density and spatial structure of TILs. Further investigation is warranted to elucidate the impact of preoperative pembrolizumab in the TME of early stage TNBC and other potential therapeutic implications. Citation Format: Rami Vanguri, Hua Guo, Shuobo Boboila, Tahsin Kurc, Han Le, Shahira Abousamra, Le Hou, Dimitris Samaras, Rajarsi Gupta, Joel Saltz, Kevin Gardner, Hanina Hibshoosh, Kevin Kalinsky, Eileen Connolly. Preoperative pembrolizumab increases sTILs in treatment naïve stage I/IIA TNBC patients in a window of opportunity trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-09-17.
Databáze: OpenAIRE
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