Inhibitory effect of semi-compatible cell transplantation on CT-26 colon cancer cells in tumorbearing mice
ZHUANSUN Xuemei1, ZHOU Qing2, SUN Maomin1
(1. Laboratory Animal Research Center, Medical College of Soochow University, Jiangsu Suzhou 215000； 2. Department of General Surgery, Affiliated Hospital of Jiangsu University, Jiangsu Zhenjiang 212013, China)
Abstract：Objective: To investigate the effect of grafts transplanted with haploidentical cells on CT-26 colon cancer cells in tumor-bearing mice and its potential mechanism. Methods: The spleen cells and bone marrow cells of C57BL/6 mice were taken as donor cells; 18 CB6F1 mice(receptor) were taken and randomly divided into control group, cyclophosphamide group and transplantation group, 6 mice in each group, and subcutaneously implanted mouse colon cancer CT26 cells to establish subcutaneous tumorbearing mouse model; then 0.2 mL of normal saline, cyclophosphamide, cyclophosphamide+spleen cells+bone marrow cells were injected into the tail vein for 4 consecutive weeks; the tumor volumes of the three groups mice were detected at different time points; tumor, liver, small intestine and skin tissues of three groups mice were harvested at 2 weeks, and the pathological changes were observed by HE staining; contents of IL2, IL-4, IL-10, IFN-γ, TNF-α and TGF-β in mouse tumor tissues were detected by ELISA. The chimerism rate of peripheral blood cells (H-2Kd/b) in the transplantation group at 3 days, 2 weeks and 4 weeks was detected by flow cytometry. Results: At the 2-week, the tumor volume in the cyclophosphamide group and the transplantation group was significantly smaller than that in the control group(both P<0.01). Compared with the control group and cyclophosphamide group, the contents of IL-2, IL-10, IFN-γ and TNF-α in tumor tissues of the transplantation group were significantly increased(all P<0.05), while the contents of IL-4 and TGF-β were significantly decreased(both P<0.05). Compared with those at 3-day, the proportion of H-2Kb in peripheral blood of CB6F1 mice was significantly increased at 2- and 4-week(both P<0.01). Conclusion: Splenocytes and bone marrow cells derived from C57BL/6(H2Kb) mice exerted an anticolorectal cancer effect on tumorbearing mice by changing the immune microenvironment of CB6F1(H-2Kd/b) mice.
Key words：
收稿日期: 2021-05-06
基金资助:
通讯作者:
孙茂民(通讯作者)，副教授，E-mail: sunmaomin@suda.edu.cn
作者简介: 颛孙雪梅(1994—)，女，硕士研究生
引用本文:
颛孙雪梅， 周庆， 孙茂民. 半相合细胞移植对CT-26结肠癌荷瘤小鼠的抑瘤作用[J]. 江苏大学学报:医学版, 2022, 32(02): 136-140.
ZHUANSUN Xuemei, ZHOU Qing, SUN Maomin. Inhibitory effect of semi-compatible cell transplantation on CT-26 colon cancer cells in tumorbearing mice. Journal of Jiangsu University(Medicine Edition), 2022, 32(02): 136-140.
［1］Brody H. Colorectal cancer［J］. Nature, 2015, 521(7551): S1.
［2］Dekker E, Tanis PJ, Vleugels Jasper LA, et al. Colorectal cancer［J］. Lancet, 2019, 394(10207): 1467-1480.
［3］Jenq RR, Van Den Brink MR. Allogeneic haematopoietic stem cell transplantation: individualized stem cell and immune therapy of cancer［J］. Nat Rev Cancer, 2010, 10(3): 213-221.
［4］Blazar BR, Hill GR, Murphy WJ. Dissecting the biology of allogeneic HSCT to enhance the GvT effect whilst minimizing GvHD［J］. Nat Rev Clin Oncol, 2020, 17(8): 475-492.
［5］Negrin RS. Introduction to the review series on “Advances in hematopoietic cell transplantation”［J］. Blood, 2014, 124(3): 307.
［6］Parmar S, Ritchie DS. Allogeneic transplantation as anticancer immunotherapy［J］. Curr Opin Immunol, 2014, 27: 38-45.
［7］Fleischhauer K, Beelen DW. HLA mismatching as a strategy to reduce relapse after alternative donor transplantation［J］. Semin Hematol, 2016, 53(2): 57-64.
［8］Carniti C, Gimondi S, Vendramin A, et al. Pharmacologic inhibition of JAK1/JAK2 signaling reduces experimental murine acute GVHD while preserving GVT effects［J］. Clin Cancer Res, 2015, 21(16): 3740-3749.
［9］Zilberberg J, Feinman R, Korngold R. Strategies for the identification of T cellrecognized tumor antigens in hematological malignancies for improved graftversustumor responses after allogeneic blood and marrow transplantation［J］. Biol Blood Marrow Transplant, 2015, 21(6): 1000-1007.
［10］Wang H, Yang YG. The complex and central role of interferonγ in graftversushost disease and graftversustumor activity［J］. Immunol Rev, 2014, 258(1): 30-44.
［11］De Casterle ID, Billiau AD, Sprangers B. Recipient and donor cells in the graftversussolid tumor effect: It takes two to tango［J］. Blood Rev, 2018, 32(6): 449-456.
［12］Renga M, Pedrazzoli P, Siena S. Present results and perspectives of allogeneic nonmyeloablative hematopoietic stem cell transplantation for treatment of human solid tumors［J］. Ann Oncol, 2003, 14(8): 1177-1184.
［13］Ghimire S, Weber D, Mavin E, et al.Pathophysiology of GVHD and other HSCTrelated major complications［J］. Front Immunol, 2017, 8: 79.
［14］Fridman WH, Zitvogel L, SautesFridman C, et al. The immune contexture in cancer prognosis and treatment［J］. Nat Rev Clin Oncol, 2017, 14(12): 717-734.
［15］Yu D, Wang L, Wu T, et al. Graftversustumor effect in major histocompatibility complexmismatched mouse liver transplantation［J］. Liver Transpl, 2019, 25(8): 1251-1264.
［16］Josephs DH, Bax HJ, Karagiannis SN. Tumourassociated macrophage polarisation and reeducation with immunotherapy［J］. Front Biosci (Elite Ed), 2015, 7: 293-308.
［17］Ruffell B, Coussens LM. Macrophages and therapeutic resistance in cancer［J］. Cancer Cell, 2015, 27(4): 462-472.
［18］Zhanna Y, Ester H, Lola W, et al. Multidonor bone marrow transplantation improves donor engraftment and increases the graft versus tumor effect while decreasing graftversushost disease［J］. Transpl Int, 2011, 24(2): 194-200.
［19］Robert S, Albring JC, Frebel K, et al. Alloantigen expression on malignant cells and healthy host tissue influences graftversustumor reactions after allogeneic hematopoietic stem cell transplantation［J］. Bone Marrow Transplant, 2018, 53(7): 807-819.
