34th Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2019): part 1
Journal for ImmunoTherapy of Cancer
Hepatocellular carcinoma (HCC) is the most common liver malignancy and the 5th cause of cancer-related mortality worldwide. Though previous studies have found that serum neutrophil-tolymphocyte ratio (NLR) is predictive of survival post liver transplant (LT), peritumoral neutrophil (PMN) infiltration in the tumor microenvironment (TME) of HCC has not been thoroughly investigated yet. In this study we sought to evaluate tissue based PMN infiltration in HCC post LT using quantitative multiplex
... unofluorescence (qmIF), previously used to study the TME of several other tumor types . Methods A database of 634 patients was created at Columbia University Irving Medical Center (CUIMC) including adult patients with available clinical follow up who underwent liver transplantation (LT) for HCC between 1998 and 2018. We evaluated a preliminary cohort of 10 patients using qmIF, excluding patients with viral hepatitis. FFPE tumor sections were pre-selected by a GI pathologist. Slides were stained using qmIF for MPO (PMNs), CD3 (T cells), CD8 (cytotoxic T cells), CD68 (macrophages), HLA-DR (immune activation), and Hep-Par1 (hepatocytes/tumor). Multiplex images were visualized using Vectra (Akoya) and processed using inForm (Akoya). Data was analyzed using R Studio for concatenation, density, nearest neighbor and statistical analysis. Serum NLR was calculated using complete blood counts collected prior to LT (Figure 1) . Results Preliminary cohort of 10 patients includes 4 with recurrence at a median of 2.4 years and 6 with no recurrence at a median of 12 years post-LT. We found that patients with recurrence post-LT have significantly higher densities of MPO+ PMNs compared to those with no recurrence. This difference is primarily driven by PMNs located within the peritumoral stroma ( Median [interquartile range [IQR] 2.46 [1.99 -2.92] vs 1.23 [0.723 -1.78], p=0.019). Intratumoral PMN infiltration was not associated with recurrence (Median [IQR] 0.91 [0.59 -1.20] vs 1.33 [0.56 -1.90], p=0.308). Moreover, density of CD3, both intratumoral and peritumoral, did not correlate with recurrence, nor did the tissue-derived NLR. Further, we found that the tissue-derived NLR did not correlate with NLR in blood. Conclusions Higher densities of peritumoral PMNs are associated with post-LT HCC recurrence. Evaluation of TME using qmIF can be used to predict recurrence in post-LT HCC. Further, tissue based analysis of PMNs does not correlate with serum NLR allowing potential for composite biomarkers. As this is preliminary, further analysis is underway and will be validated on the larger cohort of patients.