Abstract
4576 Background: In the prospective, biomarker validation HD IL-2 “Select” study, durable remissions and prolonged survival were seen in both proposed “good” and “poor-risk” patients, based on clear-cell histology subclassification and carbonic anhydrase-9 (CA-9) IHC staining. Given the toxicity and limited efficacy of HD IL-2, efforts to improve its therapeutic index are warranted. Since the high-affinity receptor of IL2 is expressed on both T regulatory cells and activated effector T lymphocytes, we explored the association between HD IL-2 response and tumor infiltration of CD8+ T and FoxP3+cells. Methods: Archival tumor tissue was collected for pathologic analysis on 120 mRCC patients enrolled in the HD IL-2 “Select” trial.Density of tumor infiltrating CD8+ T cells and Foxp3+ cells (cell/mm2) were evaluated in the invasive margin (IM) and the tumor center (TC) by IHC and automated image analysis using Aperio algorithms. The association between ORR and immune cell density was assessed using Fisher exact test. Results: Tumor specimens of 89 patients were available for analysis. 24 pts experienced response (R, including 2 CR and 22 PR) and 65 pts did not respond (NR, including 11 SD and 54 PD). Baseline patient characteristics were similar between R and NR groups. A very high density of CD8+ cells in the IM, or a high density of Foxp3+ cells in the TC were significantly associated with ORR. A stronger association with ORR was found for patients having both high density of CD8+ cells in the IM and Foxp3+ cells in the TC. Conclusions: In this prospective, biomarker validation study, response to HD IL-2 was associated with a high density of CD8+ cells in the invasive margin, and a high density of Foxp3+cells in the tumor center. Independent validation is ongoing. To improve the predictive value of Foxp3, characterization of Foxp3 expressing cells (Tregs vs activated effector T cells) in highly infiltrated tumors is underway. [Table: see text]
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