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    • br Conclusion We conducted single marker association and hap

    2021-10-09


    Conclusion We conducted single-marker association and haplotype association analyses of genetic mutations in porcine SLA-DOB and CD4 genes with T-lymphocyte subsets, cytokines, and NB-598 in pregnant Landrace sows and obtained the SNPs and insertion that significantly affected the immunity traits. We verified the possibility of using the SLA-DOB and CD4 genes as molecular markers for immune reinforcement in pregnant Landrace sows. The following is the supplementary data related to this article.
    Author contributions
    Funding This research was financially supported by the National Key Research and Development Program of China (No. 2018YFD0501000), the Beijing Innovation Consortium of Agriculture Research System (BAIC02-2016), the China Agriculture Research System (CARS-35), the National Natural Science Foundation of China (31572361), and the Program for Changjiang Scholars and Innovative Research Team in University (IRT-15R62).
    Acknowledgments
    Introduction Cancer is still one of the leading causes of death in the world, and great efforts have been made to cure it. Chemotherapy, a type of cancer treatment that uses one or more anti-cancer drugs to kill tumor cells, has long been entrusted for its high efficiency and systemic function (Chabner & Roberts, 2005). But the side effects of the cytotoxic drugs urge the emergence of new therapeutic strategy. In recent years, immunotherapy has become of great interest to researchers, clinicians and pharmaceutical companies, particularly in its promise to treat various forms of cancer with fewer side effects than existing drugs, in which immune effector cells such as lymphocytes, macrophages, dendritic cells, neutrophils and natural killer (NK) cells work together to defend the body against cancer by targeting abnormal antigens expressed on the surface of tumor cells (Syn, Teng, Mok, & Soo, 2017). Current approaches to cancer immunotherapy such as vaccine administration, adoptive cell therapies, and cytokine administration are aimed at stimulating T cells to recognize cancer antigens and develop effector mechanisms that can destroy cancer cells (Restifo, Dudley, & Rosenberg, 2012). Tumor-infiltrating T cells or T cells genetically engineered with antitumor T cell receptors (TCRs) exhibit antitumor activity, which can be adoptively transferred into patients with cancer, thus arming the patients to fight cancer with their own immune system (Rosenberg & Restifo, 2015). Nowadays, growing numbers of strategies that activate antitumor T cells straightway in vivo are applied, such as the cytotoxic T lymphocyte antigen 4 (CTLA4) inhibitor, which blocks immunoinhibitory signals and enables patients to produce an effective antitumor response, yet been approved by FDA for the adjuvant treatment of stage III melanoma and the treatment of advanced melanoma in recent years (Prieto et al., 2012). CD4+ T cells, also known as T helper cells (Th cells), play an important role in the immune system, particularly in the adaptive immune system. Additionally, CD4+ T cells alone, have been demonstrated to eliminate tumor cells. Adoptive transfer experiments using primed CD4+ T cells generated by immunization with tumor cells confer protection against a subsequent tumor challenge (Muranski & Restifo, 2009). Thus, CD4+ T cells play an important role in modulating immune responses to pathogens and tumor cells, and are important in orchestrating overall immune responses (Kennedy & Celis, 2008). Therefore, it is of great significance to elevate CD4+ T cells level and produce infiltrating CD4+ T cells in antitumor responses. β-glucans, mostly from the cell wall of cereals, bacteria and fungi, are polymers of glucoses linked by β-glycosidic bonds, mostly with β-1,3-D-backbone and β-1,6-branched glucose residues, known to possess significant biological and physiological activities and can activate the immune system (Goodridge, Wolf, & Underhill, 2009). Unlike chemotherapy drugs, β-glucans achieve good therapeutic effects with relatively low toxicities and few side effects in various diseases, particularly in cancer (Wasser, 2002; Zhang, Cui, Cheung, & Wang, 2007). The β-glucan isolated from an edible mushroom, Lentinus edodes, was first found to act as an antitumor agent against sarcoma 180 in 1969, and has been applied in clinical anticancer therapy in Japan (Chihara, Maeda, Hamuro, Sasaki, & Fukuoka, 1969; Chihara, Hamuro, Maeda, Arai, & Fukuoka, 1970). However, they have not been permitted for use in clinics worldwide due to the undefined pharmacological mechanism. To our best knowledges, intraperitoneal injection of polysaccharides is the usually used drug administration in most reported studies. In our previous work, we have demonstrated that the highly purified β-glucan from Lentinus edodes inhibits S-180 tumor growth by intraperitoneally administration at a low dose of 1 mg/kg (Xu, Zou, Xu, & Zhang, 2016; Zheng, Lu, Xu, & Zhang, 2017).