title: Inhibition of STAT3 activity re-activates anti-tumor immunity but fails to restore the immunogenicity of tumor cells in a B-cell lymphoma model.
abstract: A large number of patients with advanced lymphoma become refractory or relapse after initial treatment due to the persistence of minimal residual disease. Ideal immunotherapy strategy for eradicating the minimal residual disease of lymphoma and preventing the tendency to relapse need to be developed. Here, we use a mice model mimicked the disease entities of aggressive B-cell lymphoma dynamically to analyze the host anti-lymphoma immunity during the progression of lymphoma. We have shown that STAT3 activity was gradually enhanced in host immune effector cells with the progression of lymphoma. Inhibition of the STAT3 activity with a small molecule inhibitor was able to effectively enhance the function of both host innate and adaptive immunity, and thereby delayed the progression of lymphoma. Despite the therapeutic benefits were achieved by using of the STAT3 inhibitor, disrupting of STAT3 pathway did not prevent the eventual development of lymphoma due to the presence of point mutation of β2M, which controls immune recognition by T cells. Our findings highlight the complexity of the mechanism of immune evasion; therefore a detailed analysis of genes involved in the immune recognition process should be essential before an elegant immunotherapy strategy could be conducted.
authors.affiliation: Department of Hematology; Tongji Hospital; Tongji Medical College; Huazhong University of Science and Technology; Wuhan, Hubei PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Hematology; Tongji Hospital; Tongji Medical College; Huazhong University of Science and Technology; Wuhan, Hubei PR China.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Hematology; Tongji Hospital; Tongji Medical College; Huazhong University of Science and Technology; Wuhan, Hubei PR China.
authors.forename: Mi
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Hematology; Tongji Hospital; Tongji Medical College; Huazhong University of Science and Technology; Wuhan, Hubei PR China.
authors.forename: Danmei
authors.initials: D
authors.lastname: Xu
authors.affiliation: Cancer Biology Research Center; Tongji Hospital; Tongji Medical College; Huazhong University of Science and Technology; Wuhan, Hubei PR China.
authors.forename: Quanfu
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Department of Hematology; Tongji Hospital; Tongji Medical College; Huazhong University of Science and Technology; Wuhan, Hubei PR China.
authors.forename: Peilin
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Cancer Biology Research Center; Tongji Hospital; Tongji Medical College; Huazhong University of Science and Technology; Wuhan, Hubei PR China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Hematology; Tongji Hospital; Tongji Medical College; Huazhong University of Science and Technology; Wuhan, Hubei PR China.
authors.forename: Qinlu
authors.initials: Q
authors.lastname: Li
authors.affiliation: Cancer Biology Research Center; Tongji Hospital; Tongji Medical College; Huazhong University of Science and Technology; Wuhan, Hubei PR China.
authors.forename: Ding
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Hematology; Tongji Hospital; Tongji Medical College; Huazhong University of Science and Technology; Wuhan, Hubei PR China; Cancer Biology Research Center; Tongji Hospital; Tongji Medical College; Huazhong University of Science and Technology; Wuhan, Hubei PR China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D017354:Point Mutation; D011725:Pyridines / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction; D020032:Tyrphostins / Q000494:pharmacology; D001613:beta 2-Microglobulin / Q000235:genetics / Q000378:metabolism
chemical_list: D011725:Pyridines; D050796:STAT3 Transcription Factor; D020032:Tyrphostins; C519885:WP1066; D001613:beta 2-Microglobulin
keywords: STAT3 inhibitor; immune evasion; immunotherapy; lymphoma; β2M gene