Objective To explore the expression level of OTUB1 and its clinical significance in breast cancer.Methods Immunohistochemistry was used to detect the expression level of OTUB1 in 78 cases of breast cancer tissues and 30 cases of normal breast tissue adjacent to carcinoma,and the relationships between OTUB1 and the clinical pathological features of breast cancer were analyzed.Results The positive expression rate of OTUB1 in breast cancer tissues [66.7％ (52/78)] was significantly higher than that in adjacent normal breast tissues [30.0％ (9/30)],with a statistically significant difference (x2 =11.851,P =0.001).OTUB1 expression level was related to the lymph node metastasis (x2 =5.029,P =0.025),postoperative TNM staging (x2 =4.478,P =0.034),expression of human epidermal growth factor receptor-2 (HER-2) (x2 =8.775,P =0.003),expression of P53 (x2 =4.708,P =0.030),expression of estrogen receptor (ER) (x2 =10.364,P =0.001) and molecular subtypes (x2 =10.934,P =0.012).However,OTUB1 expression level in breast cancer was not related to the age (x2 =2.194,P =0.139),menopausal status (x2 =1.843,P =0.175),tumor size (x2 =0.643,P =0.423),histological grade (x2 =3.580,P =0.167),expression of progestin receptor (PR) (x2 =3.371,P =0.066) and expression of Ki-67 (x2 =1.345,P =0.246).Conclusion OTUB1 expression level increases in breast cancer,which is associated with the lymph node metastasis,TNM staging,expressions of HER-2,P53,ER and molecular subtypes of breast cancer.It suggests that the expression of OTUB1 is related to the progression and metastasis of breast cancer.

BACKGROUNDAdoptive cell transfer (ACT) immunotherapy has been used clinically for years to treat malignancies. Improving the killing efficiency of effector cells, such as tumor-specific cytotoxic T lymphocytes (CTLs), is an important component for enhancing the clinical response of cancer immunotherapy. Hence, we explored a novel method for preparing cancer-specific CTLs using naive T lymphocytes.

METHODSC57BL/6 mice bearing B16 melanoma tumors were pretreated with cyclophosphamide (CTX) by peritoneal injection. The immunosuppressive influence of CTX on tumor regression and the tumor microenvironment was assessed. Naive T cells and T cell pools were isolated via negative selection using immunomagnetic beads. The proliferative potential and cytokine production of different T cell subpopulations were evaluated in vitro. Tumor-specific CTLs derived from naive T cells (naive CD4+ T cells: naive CD8+ T cells = 2:1) and pooled T cells were generated in vitro, respectively. B16 melanoma-bearing C57BL/6 mice were pretreated with CTX, followed by ACT immunotherapy using dendritic cell-induced CTLs. The homing abilities of the effector cells and interleukin-2 (IL-2), interferon-γ, granzyme B, and perforin mRNA levels in tumor tissues were evaluated, and the change in tumor volume was measured.

RESULTSMice receiving CTX peritoneal pretreatment injections did not display tumor regression compared with control mice. However, a significant downregulation of splenic Tregs and tumor growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) serum levels was observed (P < 0.05). Naive T cells showed a stronger proliferative capacity and elevated cytokine production than did pooled T cells (P < 0.05). In addition, effector cells generated from naive T cells displayed more potent antitumor activity in vivo than those derived from pooled T cells (P < 0.05).

CONCLUSIONEffector cells derived from the naive T cells possess a stronger proliferative potential, homing capacity, and enhanced cytokine production, which leads to a superior antitumor response.

Animals ; Cell Line, Tumor ; Cells, Cultured ; Female ; Flow Cytometry ; Immunotherapy, Adoptive ; methods ; Melanoma, Experimental ; therapy ; Mice, Inbred C57BL