Abstract 3314: Circulatory altruistic stem cells as a prognostic biomarker for platinum based chemotherapy in oral cancer
Authors: Pathak Lekhika , Saikia Partha Jyoti , Baishya Tutumoni , Mitra Shirsajit , Pal Bidisha , Chilakamarti Ramana V. , Patra Sanjukta , Das Bikul 
Published: April 2023

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.

References:1. Bhuyan S et al. Targeting tumor stemness switch phenotype by activating pathogen induced stem cell nichedefense. 2. Talukdar J et al. Migratory cancer side population cells induces stem cell altruism in bone marrowmesenchymal stem cells to resist therapy, and enhance tumorigenic potential of non-tumorigenic cells. In: Proceedings of the 107thAnnual Meeting of the American Association for Cancer Research; . p. 920. 3. Pal B et al. Developing micro-fluidic chip to understand tounderstand altruistic stem cell reprogramming. (https://cancerres.aacrjournals.org/content/79/13_Supplement/5154). 4. Bhuyan S et al.Mesenchymal stem cell altruism mediates a novel HMGB1/NKG2D immune response in oral cancer(https://doi.org/10.1158/1538-7445.AM2020-5539).5. Pathak L, Gayan S, Pal B, Talukdar J, Bhuyan S, Sandhya S, Yeger H, Baishya D, Das B*.Coronavirus Activates an Altruistic Stem Cell-Mediated Defense Mechanism that Reactivates DormantTuberculosis: Implications in Coronavirus Disease 2019 Pandemic. Am J Pathol. 2021

Citation Format: Lekhika Pathak, Partha Jyoti Saikia, Tutumoni Baishya, Shirsajit Mitra, Bidisha Pal, Ramana V. Chilakamarti, Sanjukta Patra, Bikul Das. Circulatory altruistic stem cells as a prognostic biomarker for platinum based chemotherapy in oral cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3314.