W159 - Immunological Correlates of Successful Treatment of Stage IV Pulmonary Lymphoepithelioma-like Carcinoma (LELC) with Adoptive EBV-specific T Cell Immunotherapy

Shuting Han – National Cancer Centre Singapore; Timothy Shuen – National Cancer Centre Singapore; Who-Whong Wang – National Cancer Centre Singapore; Rebecca Ba – National Cancer Centre Singapore; Ahmad bin Mohamed Lajam – Singapore Health Services; Dianyan Guo – Singapore Health Services; Han Chong Toh – National Cancer Centre Singapore; Salvatore Albani – Singapore Health Services

Abstract Text: Pulmonary lymphoepithelioma-like carcinoma (pLELC) is associated with Epstein-Barr virus (EBV) infection. A stage IV pLELC patient was treated with EBV-CTLs as part of a compassionate drug access programme. Adoptive T cell therapy was carried out following chemotherapy. The patient went into full remission but eventually relapsed. We aimed to assess systemic immunologic changes in this patient associated with treatment response and subsequent relapse. Peripheral blood from 7 treatment intervals were profiled using mass cytometry and analysed using the Extended Polydimensional Immunome Characterisation (EPIC) discovery tool. Treatment resulted in dramatic decline in plasma EBV DNA titre, a known indicator of clinical outcome, and near complete metabolic response. Upon relapse, EBV DNA titres rebounded. Decreasing EBV titre was correlated with decreased circulating Ki-67+ CD27+ memory B cells (R2=0.76, p=0.01), which may reflect concomitant targeting of endogenously infected B cells by EBV-CTL. By contrast, the frequency of CD27- CXCR5- naive B cells (R2=0.88, p=0.002) was inversely correlated with EBV titre, possibly replacing the depleted memory B cell population. Clinical outcome in response to EBV-CTL treatment is thus reflected both in plasma EBV DNA titres and the circulating immunome. Our case study demonstrates for the first time the clinical benefit of chemotherapy + EBV-CTLs in pLELC and the utility of monitoring plasma EBV DNA titres in this treatment. Further studies in larger cohorts will determine the functional contribution of these immune subsets to disease control and specific interactions of EBV-CTL with the immune system.