Abstract B02: Immune events in the sentinel lymph node in melanoma predict local and systemic response to disease

Abstract

Abstract Background: The sentinel node (SN) has become the standard diagnostic tool for staging cutaneous melanoma. With the recent development of anti-CTLA-4 and anti-PD-1 antibodies as immunotherapies we hypothesized that the early immune events in melanoma maybe first observed in the SN and be related to the response to disease. Methods: 81 SN from 79 patients were evaluated with microarray technology, qPCR, routine H&E & IHC. We identified 10 immune genes that are present by qPCR in SNs from a random section of the SN. Statistical analysis assessed the utility of these markers to predict tumor-positive SN and survival. Results: Of the 79 patients, 48 (61%) were men. Median age was 59 (range 6-95 years). Primary melanomas were most commonly from the trunk (51%) and extremities (40%). The median thickness of the primaries was 0.95mm. 13% of the patients had ulcerated primaries. 29% of the primary tumors had at least 1 mitosis/mm2 . 9 (11%) patients had SN metastasis, as determined by conventional H&E and IHC. The incidence of SN positivity was directly related to tumor thickness; the higher the T-stage the greater percentage of SN positivity: 2% T1, 19% T2, 20% T3 and 60% T4 melanoma. 33% of ulcerated primaries and 30% with increased mitotic rate had a tumor-positive SN. The microarray did not identify specifc immune related genes when comparing tumor-positive to tumor-negative SN. We then evaluated the gene expression of CD80, CD86, CD28, CD40, IDO, Arginase, IL-2, IL-10, PD-1 and CTLA-4 by qPCR. By univariate analyses: patient age (p<0.001), primary site (<0.001), decreasing gene expression of CTLA-4 (p<0.001) and PD-1 (p<0.001) in SN were predictive of SN positivity. Multivariate analyses confirmed the down-regulation of CTLA-4 and PD-1 gene expression in the SN were predictive of metastases in the SN and the AUC values of predicting SN positivity were 0.808 and 0.731 respectively . The positive and negative predictive values of the tests were 100 and 89.5%. Further the down-regulation of CTLA-4 and PD-1 gene expression in the SN correlated with diminished survival, while the up-regulation of IL-10 correlated with poor survival. Conclusions: Our results demonstrate the significance of CTLA-4, PD-1 and IL-10 gene expression in the SN of melanoma patients. The expression of these genes may be early events in the immune dysfunction that occurs with melanoma metastases. Citation Format: Richard Essner, Ke-Wei Gong, David Z. Kaufman, Alexandra Gangi, Myung Shin Sim. Immune events in the sentinel lymph node in melanoma predict local and systemic response to disease. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr B02.