Transcriptomic and Immunophenotypic Characterization of Tumor Immune Microenvironment in Squamous Cell Carcinoma of the Oral Tongue

The tumor immune microenvironment of oral tongue squamous cell carcinoma may be accountable for differences in clinical behavior, particularly between different age groups. We performed RNA expression profiling and evaluated tumor infiltrating lymphocytes (TILs) and their T-cell subsets in order to assess the functional status of oral tongue squamous cell carcinoma tumor microenvironment and detect potentially clinically useful associations. Archival surgical pathology material from sixteen oral tongue squamous cell carcinoma patients was microscopically evaluated for TIL densities. RNA was extracted from macrodissected whole tumor sections and normal controls and RNA expression profiling was performed by the NanoString PanCancer IO 360 Gene Expression Panel. Immunostains for CD4, CD8 and FOXP3 were evaluated manually and by digital image analysis. Oral tongue squamous cell carcinomas had increased TIL densities, numerically dominated by CD4 + T cells, followed by CD8 + and FOXP3 + T cells. RNA expression profiling of tumors versus normal controls showed tumor signature upregulation in inhibitory immune signaling (CTLA4, TIGIT and PD-L2), followed by inhibitory tumor mechanisms (IDO1, TGF-β, B7-H3 and PD-L1). Patients older than 44 years showed a tumor microenvironment with increased Tregs and CTLA4 expression. Immunohistochemically assessed CD8% correlated well with molecular signatures related to CD8 + cytotoxic T-cell functions. FOXP3% correlated significantly with CTLA4 upregulation. CTLA4 molecular signature could be predicted by FOXP3% assessed by immunohistochemistry (R² = 0.619, p = 0.026). Oral tongue squamous cell carcinoma hosts a complex inhibitory immune microenvironment, partially reflected in immunohistochemically quantified CD8 + and FOXP3 + T-cell subsets. Immunohistochemistry can be a useful screening tool for detecting tumors with upregulated expression of the targetable molecule CTLA4.Electronic supplementary materialThe online version of this article (10.1007/s12105-020-01229-w) contains supplementary material, which is available to authorized users.     

New insights into tumor-host interactions in lymphoma metastasis

The metastatic process is characterized by a complex series of sequential steps involving constant interactions (mutual cross-talks) of metastasized tumor cells with their microenvironment (lymphocyte, macrophages, endothelial cells, etc.) in target organs. These interactions determine the outcome of metastasis (either the eradication of metastatic cells or their increased proliferation and invasion). Recently developed methods of tumor and host cell analysis at the molecular level allow better elucidation of molecular mechanisms of metastasis and of immune mechanisms involved in antitumor responses. Direct modulation of these processes will probably increase the success of clinical cancer treatment. Here we review data (a) on the expression of some costimulatory (MHC class II, CD80, sialoadhesin) and adhesion (LFA1, ICAM-1, VLA-4) molecules on both metastasized tumor cells and host cells and (b) on the production of a cytotoxic molecule, nitric oxide, by in situ activated Kupffer and endothelial cells in the process of liver metastasis. This study was performed with well-characterized murine ESbL T lymphoma cells transduced with the bacterial lacZ gene, which allows detection and quantification of metastases at the single cell level throughout lymphoma growth and metastasis. Experimental results are discussed in the context of recent literature.Abbreviations APC Antigen-presenting cells - hCRP Human C-reactive protein - ICAM Intercellular adhesion molecule - IFN Interferon - IL Interleukin - iNOS Inducible NO synthase - LFA Leukocyte function associated antigen - SER Sheep erythrocyte receptor - TA Tumor-associated rejection antigens - TNF Tumor necrosis factor - VCAM Vascular cell adhesion molecule - VLA Very late activated antigen     

梨状窝癌局部扩展的病理学研究

目的　探讨梨状窝癌局部扩展的规律 ,为梨状窝癌的手术治疗提供病理学依据。方法　应用石蜡包埋大体标本连续切片的方法 ,对 2 6例梨状窝癌全喉及次全喉切除的标本进行了观察。结果　位于梨状窝外侧壁的肿瘤 ( 4例 )主要向外侧咽侧壁扩展 ,位于梨状窝内侧壁的肿瘤 ( 5例 )容易向喉腔及对侧梨状窝扩展。累及整个梨状窝 17例。声门旁间隙及甲状软骨是最易受侵犯的喉结构 ,环状软骨受侵较少 ;会厌及会厌前间隙的侵犯未见超过中线 ,声门旁间隙及会厌前间隙的侵犯途径有2个 ,肿瘤沿杓会厌襞向前及在甲状软骨板内侧直接向前侵犯声门旁间隙 ;肿瘤沿杓会厌襞向内上方及在甲状软骨板内侧上部侵入会厌前间隙。结论　会厌前间隙的受侵并不是喉部分切除的禁忌证 ,大部分位于梨状窝外侧壁的肿瘤及部分梨状窝内侧壁的肿瘤保留喉功能是可行的 ;位于梨状窝内侧壁及环后区的肿瘤易在环后区向对侧侵犯 ,对累及环后区的梨状窝癌 (Ⅰ ,Ⅲ型 ) ,应注意肿瘤在环后区粘膜下向对侧侵犯。     

P^27的研究概况

目的：综述Ｐ＾２７的研究进展。方法：光盘检索有关献,归纳综合整理。结果：Ｐ＾２７是细胞周期的相关蛋白,Ｐ＾２７白过度表达可抑制细胞周期的进程,阻断细胞生长于Ｇ１期。结论：Ｐ＾２７是细胞周期中重要的负性调控控因子,是一种新的侯选的肿瘤抑制基因。     

Excretion of modified nucleosides during development of malignant lymphomas in mice after whode body irradiation

Summary During x-ray-induced development of malignant lymphomas in mice their urinary excretion of eight modified nucleosides was monitored and the values were compared to the results of the histological examination of the animals at time of their sacrifice.It was found that the pathologically augmented excretion of modified nucleosides begins as much as several weeks before the malignant lymphomas can be diagnosed clinically. Thus some mice had increased levels of modified nucleosides even 10 weeks before sacrifice, though at the time of sacrifice the histological investigation reveled only some small foci of reticulum cell neoplasm in their spleen.It is therefore stressed that the usefulness of the determination of urinary modified nucleosides as an early noninvasive screening test for cancer in man and as an in vivo carcinogenicity test should be evaluated.Abbreviations pseudouridine - m¹A 1-methyladenosine - m⁵C 5-methylcytidine - m¹I 1-methylinosine - m¹G 1-methylguanosine - m²G N ²-methylguanosine - m²G N ²,N²-dimethylguanosine - ac⁴C N ⁴-acetylcytidine - mt⁶A N-(9--d-ribofuranosylpurine-6-yl)N-methylcarbamoyl) threonine - acp³U 3-(3-amino-3-carboxypropyl) uridine - SD standard deviation     

DMBA-induced tumors and their prevention by aromatic retinoid (Ro 10-9359)

Summary Both auricles of 21 domestic rabbits were painted with dimethylbenz-anthracene (DMBA). Eleven animals of this group were additionally fed aromatic retinoid (AR) by an esophageal tube. Two control animals were not treated at all.Eight or 9 weeks after the beginning of the study six of the seven remaining animals, which had only been painted with DMBA, developed a total of 25 keratoacanthoma-like tumors (KA). On the other hand, none of the seven animals left, which were painted with DMBA and fed AR showed any tumor by this time.The systemic effect of AR was studied in biopsies from the snout and the back. The epidermis of the snout showed mucous mataplasia by histochemical and electron-microscopic criteria, whereas the epidermis of the back was not significantly altered. The production of intra- and extracellular lamellated material indicated an additional effect of AR on epidermal lipid metabolism. The effect of AR in the prevention of DMBA-induced tumors was characterized by mucoid cytolysis and karyolysis.Supported by the Deutsche Forschungsgemeinschaft (Ma 674/3-2)     

Effects of interleukin-1, tumor necrosis factor-β, and forskolin on tissue plasminogen activator activity in human osteoblastic osteosarcoma cells

Summary The effects of interleukin-1 (IL-1), forskolin, and tumor necrosis factor (TNF-) on tissue plasminogen activator (t-PA) activity were studied in the human osteoblastic osteosarcoma cell line, G292. t-PA activity was measured in the cell media using the chromogenic substrate, S-2251. After a 24 hour incubation period, IL-1 increased t-PA in a dose-dependent manner. The effect of IL-1 at 10.0 U/ml was partially inhibited in the presence of indomethacin. Forskolin (1.0 M) increased t-PA activity after 24 hours with the effects of combined treatment of IL-1 (1.0 U/ml, 10.0 U/ml) and forskolin being apparently additive in nature. TNF- (10^-8–10^-7 M) also produced increased t-PA activity in the cell medial after a 24 hour incubation period. These results suggest that the cytokines, IL-1 and TNF-, can increase t-PA activity in G292 cells and that there is both a cAMP-dependent as well as a cAMP-independent pathway involved in the regulation of this osteoblastic cell function.     

Mutagenicity studies with praziquantel,a new anthelmintic drug: Tissue-, host-, and urine-mediated mutagenicity assays

Praziquantel, a new anthelmintic drug with activity against all species of schistosomes pathogenic to man, and against a wide range of Cestodes, was tested for mutagenic potential. For the detection of both base substitutions and frameshift mutations, Salmonella typhimurium TA 100 and TA 98 were used as tester strains. Using the plate assay with and without added S-9, host-mediated assay and urine-mediated assay without and after incubation with -glucuronidase/arylsulfatase, no mutagenic activity could be detected.     

IL-2活化瘤苗对胃癌术后复发和转移的抑制作用

目的观察用细胞因子活化的特异性瘤苗辅助常规化疗,治疗外科手术后临床Ⅲ～Ⅳ期胃癌患者,抑制肿瘤术后复发、转移的临床疗效。方法于外科术后常规化疗结束后2周,用患者自体肿瘤细胞抗原致敏、IL-2活化的树突状细胞(DC)作为瘤苗给患者四肢皮下多点免疫注射1×106/(ml·次),每周1次,每疗程注射4次,0.5年后强化1次。定期胃镜、影象学和肿瘤标志物检查,随访至手术后第2年,观察生存期和生存率。结果经瘤苗治疗后,患者的免疫功能显著改善。术后24个月,瘤苗联合化疗组患者的生存率为50%,血清中CEA和CA724分别为(10±1.5)ng/ml和(5.5±1.5)U/ml,而单纯化疗组患者的生存率为10%,CEA和CA724的水平分别为(77.0±9.4)ng/ml和(55.0±7.6)U/ml;P<0.001。结论特异性瘤苗免疫治疗,能增强胃癌患者术后的特异性抗肿瘤免疫功能,提高手术后化疗疗效,抑制肿瘤复发和转移,能延长患者生存期,提高生存率。