TY - JOUR T1 - CD38 is a good predictor of anti-PD-1 immunotherapy responsiveness in hepatocellular carcinoma JF - bioRxiv DO - 10.1101/638981 SP - 638981 AU - Siting Goh AU - Harry Ho Man Ng AU - Valerie Chew AU - Xin Ni Sim AU - Huihua Li AU - Sherlly Lim AU - Jeffrey Chun Tatt Lim AU - Josh Jie Hua Loh AU - Khin Sabai AU - Clara Chong Hui Ong AU - Tracy Loh AU - Wei Qiang Leow AU - Joycelyn Lee Jie Xin AU - Han Chong Toh AU - Fabio Malavasi AU - David Wai Meng Tai AU - Ser Yee Lee AU - Pierce Chow AU - Evan Newell AU - Su Pin Choo AU - Joe Yeong AU - Tony Kiat Hon Lim Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/05/15/638981.abstract N2 - Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated mortality in the world. However, with the associated low five-year survival and high recurrence rates, alternative treatment modalities specifically immunotherapy have been researched. A correlation between CD38+ tumour-infiltrating leukocyte (TIL) density and improved prognosis was found in a recent study. However, studies relating to CD38 expression in immune infiltrates within tumours are limited. In the present study, we confirmed the expression of CD38 on macrophages in HCC and determined the relationship between CD38+ leukocytes and lymphocytes and patient response to immunotherapy. Using immunohistochemistry, we analysed tissue samples obtained from 20 patients from Singapore with HCC prior to immunotherapy. Tumour infiltrating leukocytes expression within tumour were correlated to the responsiveness of patients to immunotherapy.Expression of CD38 was found within the tumour cells and surrounding immune infiltrates including lymphocytes and macrophages. We then ask whether CD38 expression by the distinct cell populations may acquire theranostic relevance. Patients with higher level of CD38+ immune infiltrate subsets had significantly better response to anti-PD-1 immunotherapy, and this is also true for CD38+ lymphocytes within the tumour microenvironment. In particular, a cut-off of 13.0% positive out of total leukocytes and 12.4% positive out of total lymphocytes is found to be of strong predictive value of responsiveness to immunotherapy treatment, thus a strong theranostic impact is seen by using CD38 as a biomarker for anti-PD-1 therapy.The establishment of an association between CD38 expression and the response to anti-PD-1 immunotherapy in HCC, could be applied to a larger cohort outside Singapore. These may eventually change the routine testing in clinical practice to identify HCC patients suitable for immunotherapy. ER -