Lola Milanese
Research Mentor(s): Lauren Krumeich
Mentor Department: Surgery
Authors:
Session: Session 5 (2:00pm – 2:50pm)
Presentation Type: Poster 61
Abstract
Background: Non-small cell lung cancer (NSCLC) is the most fatal malignancy in the United States and often metastasizes to the adrenal gland. Checkpoint inhibition promotes an anti-tumor response against NSCLC but is less effective in the adrenal gland. The adrenal gland is the predominant producer of glucocorticoids, known immunosuppressants. We hypothesize that the glucocorticoids in the adrenal gland correlate with reduced immune response in adrenal metastases of NSCLC, therefore promoting tumor growth. Methods: We injected LLC1 (KRAS G12C) and KPL86 (KRASG12D/p53) NSCLC cell lines into the lung and adrenal gland of 24 B6 mice to characterize their tumor infiltrate using flow cytometry (CD4, CD8, PD1, FOXP3, CD45) and immunohistochemistry (CD3, CD4, CD8, PDL1, CD163, CD68, FOXP3). We obtained pathologic samples from patients who underwent lung resections and adrenalectomies for metastatic NSCLC through Michigan Medicine for evaluation with multiplex immunohistochemistry (CD3, CD8, FOXP3, CD163, PDL1). Results: Gross tumor growth was identified in the lung and adrenal glands of all 24 mice 2 weeks after orthotopic injection. We have harvested bilateral lungs and adrenal glands from 6 mice and embedded the tissue for immunohistochemistry. We have performed single cell suspension from 8 B6 mice in preparation for flow cytometry. Multiplex immunohistochemistry from 4 human specimens demonstrates significant variability in the immune infiltrate between lung and adrenal specimens of the same patient and between adrenal specimens from different patients. Quantification is in process. Conclusion: We have demonstrated proof of concept of orthotopic injections in the lung and adrenal glands with 100% efficacy in a B6 mouse model. We have also demonstrated significant heterogeneity in the immune infiltrate of human pathologic specimens harboring NSCLC, supporting a potential role of immune variability in promoting metastatic NSCLC in the adrenal gland.
