O1.03 * DENSITY OF TUMOR INFILTRATING LYMPHOCYTES CORRELATES WITH BRAIN EDEMA AND OVERALL SURVIVAL IN BRAIN METASTASES

Abstract

BACKGROUND: Density of tumor-infiltrating lymphocytes (TILs) has a prognostic impact in various extracranial solid tumors. While a favorable correlation of CD3+ effector TIL, CD8+ cytotoxic TIL and CD45RO+ memory TIL density was observed, high density of FOXP3+ regulatory TILs is associated with impaired survival prognosis in previous studies of primary extracranial solid tumors. So far, TILs have not been analyzed in brain metastases (BM) from solid tumors. METHODS: 118 BM specimens (primary tumor: lung cancer (62/118; 52%); breast cancer (17/118; 14%); melanoma (6/118; 5%); kidney cancer (10/118; 8%); another primary tumor (23/118; 19%)) were available. All patients had one single BM and received neurosurgical resection as first treatment for BM. Preoperative MRT was available in all patients. Clinical data was retrieved by chart review. Overall survival (OS) was defined as time from first diagnosis of BM to last follow up or death. Analysis of for CD3, CD8, CD45RO and FOXP3 was performed by immunohistochemical methods on full section slides and analyzed using previously published semiquantitative evaluation criteria. RESULTS: Dense infiltration with CD3+ TILs was observed in 64/118 (54%) specimens, with CD8+ TILs in 70/118 (59%), with CD45R0+ TILs in 72/118 (61%) and with FOXP3+ TILs in 26/118 (22%) specimens. Dense CD3+ TILs infiltration was more frequently observed in lung cancer, melanoma and kidney cancer BM than in breast cancer BM (p = 0.024; Chi square test). Melanoma BM had more frequently dense infiltration with FOXP3+ TILs (p = 0.003; Chi square test). Density of CD3 + , CD8 + , CD45RO + , or FOXP3+ TILs did not correlate with preoperative steroid application (p > 0.05; Chi Square test). Patients with dense infiltration of CD3+ TIL had significantly improved OS (27 vs. 12 months; p = 0.002; log rank test). Further, dense infiltration with CD8+ TILs was associated with improved OS (16 vs. 12 months; p = 0.048; log rank test) and large peritumoral edema on the preoperative MRI (p = 0.03; Chi Square test). Dense infiltration with CD45RO+ TILs was correlated with improved survival prognosis (18 vs. 8 months; p = 0.01; log rank test). Patients with dense infiltration of FOXP3+ TILs had an impaired survival prognosis (6 vs. 16 months; p = 0.05; log rank test). A composite “immuno score” showed a strong association with median OS (27 months for cases CD8 + /CD45RO + /FOXP3- infiltrates and 6 for cases with CD8-/CD45RO-/FOXP3+ infiltrates; p = 0.001 log-rank test). CONCLUSION: Dense TILs infiltrates are common in BM and correlate with the amount of peritumoral brain edema and improved survival prognosis. Further studies should investigate the therapeutic impact of immunomodulatory agents in patients with BM.