Myeloid antigen-presenting cell niches sustain antitumor T cells and license PD-1 blockade via CD28 costimulation

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Multi-phenotype CRISPR-Cas9 Screen Identifies p38 Kinase as a Target for Adoptive Immunotherapies

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Stromal Tumor Infiltrating Lymphocytes (sTILs) Were Associated with a Higher Grade and a Lower Stage of Indonesian Triple Negative Breast Cancers

Objective: This study aimed to investigate the association of sTILs with clinicopathological parameters and overall survival (OS) in patients with triple negative breast cancer (TNBC). Methods: One hundred and twenty-five paraffin embedded tissue of patients with TNBC, collected from Dr. Sardjito General Hospital Yogyakarta, Indonesia, between 2008-2017, were used in this study. Stromal TILs were examined from hematoxylin and eosin (H&E)-stained samples, and classified as either low or high score using 20% cut-off. Analysis of the association of sTILs with clinicopathological parameters, relative risk (RR) and OS used 95% confidence interval (CI) with significance set as p<0.05. Results: The higher proportion of TNBC patients in this study were ≥40 years old (83.3%), high tumor grade (68%), tumor stage >IIIa (56%), alive (50.4%), and with low sTILs (54.4%). The results showed significant association between sTILs and a higher grade or a lower stage of tumor (B = 0.259, 95%CI = 0.090-0.468, p = 0.004 and B = -0.255, 95%CI = -0.433 - -0.080, p = 0.005, respectively ). Meanwhile sTILs were not associated with age at diagnosis (B = 0.027, 95%CI = -0.193 – 0.264  p = 0.758 nor 3-year OS of patients (HR = 0.342, 95%CI = 0.41 - 1.43  p = 0.402). Conclusion: The results indicate that sTILs may serve as an additional pathological parameter for TNBC.     

早、晚期胃癌肿瘤浸润免疫细胞的形态学研究

目的　探讨人早、晚期胃癌肿瘤浸润免疫细胞的形态学特征。方法　通过免疫组织化学、光镜和电镜的方法观察人早、晚期胃癌肿瘤浸润免疫细胞的分布和形态学变化。结果　肿瘤浸润树突状细胞 (TIDC)主要分布在癌周区 ,病变早期TIDC比病变晚期数量多 (P <0 .0 1)。肿瘤浸润淋巴细胞 (TIL)主要分布在癌交界区和癌周组织 ,病变早期TIL比病变晚期数量多 (P <0 .0 1)。电镜下 ,TIDC体积较大 ,形态不规则 ,表面有许多树枝状突起 ,细胞核不规则 ,可见核仁 ,胞质内有丰富的线粒体、核糖体、高尔基复合体和内质网。TIDC与TIL和肿瘤细胞接触方式和形式上呈多样性。一对一 ,一对多 ,或形成簇的接触方式。有紧密膜接触、指状膜接触和球状膜接触形式。结论　本实验提示TIDC和TIL数量多少与肿瘤的进展有关 ,TIDC与TIL和肿瘤细胞之间关系密切     

4-1BB （CD137） Ligand Enhanced Anti-Tumor Immune Response against Mouse Forestomach Carcinoma In Vivo

Cancer occurrence and development has been demonstrated to be associated with escape from immune surveillance, and low eostimulatory molecules expression has been considered as one of the important reasons for cancer evading the immune system. 4-1BB （CD137） is a costimulatory molecule expressed on the surface of activated T cells. Interaction of 4-1BB with its natural ligand （4-1BBL） expressed on antigen presenting cells （APCs） has been shown to amplify T-cell mediated immunity. We therefore examined whether murine cancer cells expressing 4-1BBL could produce antitumor effects in inoculated mice. Mouse forestomach carcinoma （MFC） cells were transfected with 4-1BBL gene （MFC/4-1BBL）. The proliferation of the transduced cells in vitro was not different from that of parental cells. However, MFC/4-1BBL cells developed small tumors and induced higher cytotoxicity of tumor infiltration lymphocyte （TIL）. Production of cytokines （IFN-γ TNF-α and IL-2） in serum and cytotoxic T lymphocyte （CTL） activity of splenocytes from mice immunized with mitomycin C （MMC）-treated MFC/4-1BBL cells were significantly higher than that from mice immunized with MMC-treated parental MFC and MFC/ pMKITneo cells. These results suggest that modification of cancer cells with 4-1BBL gene can produce antitumor immune responses.     

个体骨转移瘤化疗药物筛选在肿瘤浸润淋巴细胞免疫治疗中的应用

作者自1989～1991年间,设计具有特异性的个体骨转移瘤化疗药物筛选并应用于肿瘤浸润淋巴细胞的过继免疫治疗临床。测试药物为长春新碱、阿霉索、顺铂、氨甲喋呤、氟脲嘧啶、丝裂霉素等6种,计138次敏感性试验,实验总有效敏感率为31.88%,临床按mg/m~2/W 常规剂量用药,有效率为47.83%(P<0.01)。