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Research & Publication
Dr. Mohammad Zahedul Alam
Alam Zahedul Md. (), "Credit card marketing at Rajshahi Metropolitan City: Present status, Problem and Prospects" Journal of Institute of Bangladesh Studies, volume:
Alam Zahedul Md. (), “Credit card marketing in Bangladesh: Present status, problems and prospects”. Management Trends, A journal of Department of Business Administration, Saurashtra University, India, pp
Alam Zahedul Md. (), “SWOT analysis of Pharmaceutical Industry: A Study of some selected Firms in Bangladesh” Journal of Institute of Bangladesh Studies, volume: 33, University of :
Alam Zahedul Md & Nufur Jannatul Mawa ()” Job holders’ attitudes towards credit card in Bangladesh-A study on some selected credit card providers in Bangladesh”, COSMOS, A compilation of Research Papers on Contemporary Issues in Commerce Management and Economics, M.C.E. Society’s Abeda Inamdar Senior. College of Arts, Science and Commerce, Pune, India, pp
Alam Zahedul Md & Eva Meherunnessa ()” Private Universities in Bangladesh: An Analysis of their Growth and Development”, COSMOS, A compilation of Research Papers on Contemporary Issues in Commerce Management and Economics, M.C.E. Society’s Abeda Inamdar Senior. College of Arts, Science and Commerce, Pune, India, pp
Alam Md. Zahedul & Habib Md. Anamul () “Business Analysis of Pharmaceutical Firms in Bangladesh: Problems and Prospects” Journal of Business and Technology (Dhaka), Norhtern University Bangladesh, Volume-VI, Issue-1, pp
Alam Zahedul Md, Rana Sohel (), Customers’ attitudes towards retail chain store services in Bangladesh – A comparative study between retail chain store and small retail store, ” Journal of Business Studies, Faculty of Business Studines, Universitiy of Rajsha hi, Volume No: 5 pp
Alam Zahedul Md. Zaman Farhana () Business Analysis of Real Estate Sector in Bangladesh: Problems and Prospects-A study on Dhaka city, Journal of Business Studies, Faculty of Business St
Mowat et al. show that anti-tumor immunity in dMMR CRCs relies on recruitment and retention of systemic CD8 T cells. This is driven by extensive genomic instability that upregulates CCL5 and CXCL10 in the CRC cells by endogenously activating cGAS/STING and type I IFN signaling.
Abstract
Colorectal cancers (CRCs) deficient in DNA mismatch repair (dMMR) contain abundant CD8 tumor-infiltrating lymphocytes (TILs) responding to the abundant neoantigens from their unstable genomes. Priming of such tumor-targeted TILs first requires recruitment of CD8 T cells into the tumors, implying that this is an essential prerequisite of successful dMMR anti-tumor immunity. We have discovered that selective recruitment and activation of systemic CD8 T cells into dMMR CRCs strictly depend on overexpression of CCL5 and CXCL10 due to endogenous activation of cGAS/STING and type I IFN signaling by damaged DNA. TIL infiltration into orthotopic dMMR CRCs is neoantigen-independent and followed by induction of a resident memory-like phenotype key to the anti-tumor response. CCL5 and CXCL10 could be up-regulated by common chemotherapies in all CRCs, indicating that facilitating CD8 T cell recruitment underlies their efficacy. Induction of CCL5 and CXCL10 thus represents a tractable therapeutic strategy to induce TIL recruitment into CRCs, where local priming can be maximized even in neoantigen-poor CRCs.
Introduction
Colorectal cancer (CRC) is a prevalent and often fatal disease initiated by loss of either the tumor suppressor APC or the DNA mismatch repair gene MLH1 (Kloor and von Knebel Doeberitz, ; Picard et al., ). Whereas APC inactivation promotes large-scale DNA damage leading to chromosomal instability (CIN), MLH1 inactivation promotes hypermutability in the form of genome-wide point mutations and microsatellite instability (MSI) from deficient mismatch repair (dMMR). Although accounting for only 10–15% of CRCs, dMMR CRCs are of particular interest due to .