Abstract Background: Head & neck cancer is the 4th common cancer, and most of them are diagnosed late, andtreated with cisplatin monotherapy. In these subsets of patients, immunotherapy has been tried, butwithout major success [1]. We speculate that circulating altruistic mesenchymal stem cells may serve asbiomarker for immunosuppression. Previously, we showed that oral cancer CSCs reprogram MSCs toaltruistic phenotype [2, 3], an embryonic stem cell like phenotype having niche defending ability [5].Here, we propose to test the immunosuppressive ability of ASCs, and their detection in the circulation ofhead & neck cancer subjects undergoing platinum based chemotherapy. Method: The immunosuppression test: immunosuppressive secretory factors, mixed lymphocytereaction (MLR) assay, and a Boyden chamber based co-culture assay with NK cells [4]. Next, weobtained circulating CD271+/CD45- cells of stage IV head and neck cancer subjects (n=20) (5). Kaplan-Meier survival analysis and log-rank test to find association between the presence of circulatory ASCsand overall survival (OS). Result: CSCs including primary tumor obtained CSCs reprogram CD271+ MSCs to ASC phenotype;these cells secrete high level of Nitric oxide, IDO, TGF-beta, IL-10 and PGE-2. ASCs exhibited markedimmunosuppression in the MLR test. In Boyden chamber assay, ASCs markedly decreased the numberof NKG2D+ NK cells, and CD8+ T cells by 4-5 fold, whereas increased the CD4+/FoxP3/CD25- T-reg cells by 3-fold . Importantly, these 12 out of 20 patients showed poortreatment response to platinum therapy. The OS at 6 months was 24.6% for circulating ASC-positivepatients and 47.4% for circulating ASC- negative patients (log-rank test,). Conclusion: The circulatory ASCs could be a promising biomarkers for immunotherapy.