慢性萎缩性胃炎和胃癌患者T细胞亚群及NK细胞活性的检测研究

 本文用OKT单抗致敏血球花环法和MTT比色法对慢性萎缩性胃炎(CAG)和胃癌(GC)患者进行外周血T淋巴细胞亚群及NK细胞活性的检测。结果显示CAG患者CD⁺₃亚群及CD₄/CD₈均较健康对照明显降低(P<0.01),NK细胞活性显著低下(P<0.01)。胃癌患者术前CD⁺₃、CD⁺₄亚群及CD₄/CD₈较健康对照明显降低(P<0.01),CD⁺₈亚群显著升高(P<0.01),NK细胞活性明显升高(P<0.01)。与CAG患者比较,胃癌患者术前CD⁺₃亚群及CD₄/CD₈明显降低(P<0.05),CD8+亚群显著升高(P<0.01),NK细胞活性显著低下(P<0.01)。而术后两周,以上指标有不同程度的恢复,说明CAG患者的细胞免疫功能已处于失调状态,而胃癌患者的免疫失调更为严重,但手术切除肿瘤后病人的免疫失调能迅速恢复,一般为两周左右。     

肺癌化疗中胸腺肽(Thymopeptides)治疗的作用评价

 168例晚期肺癌患者, 分对照和处理二组, 对照组单用化疗, 处理组在化疗同时合并使用胸腺肽。 治疗前后均测定外周血T淋巴细胞亚群(CD₃、CD₄、CD₈以及T₄/T₈比)和IgG、Iga、IgM。 同时评判生活质量(kps)及观察胸片上癌灶变化。 结果表明, 胸腺肽对提高患者细胞免疫功能有显著意义, 但对癌灶的缩小无明显作用。     

脑胶质瘤患者自体免疫治疗前后T细胞亚群的变化

 目的 探讨脑胶质瘤患者自体免疫治疗的临床应用，观察该治疗对T细胞亚群水平的影响。方法 试验组21例脑胶质瘤患者接受自体树突状细胞免疫治疗，对照组19例接受常规治疗，进行临床随访并检测两组T细胞亚群水平的变化。结果 试验组中位生存时间（29个月）远大于对照组（10个月），两组生存曲线分布差异有显著性意义（P〈0．05）。脑胶质瘤患者外周血中CD^3＋含量、CD^4＋含量以及CD^4＋／CD^8＋比值明显低于正常对照组（P〈0．01），免疫治疗后患者外周血CD^3＋、CD^4＋、CD^8＋含量以及CD^4＋／CD^8＋比值与对照组比较均增加（P〈0．05），但CD^4＋／CD^8＋比值仍低于健康成人组（P〈0．05）。结论 脑胶质瘤存在免疫功能抑制，自体树突状细胞肿瘤疫苗治疗可一定程度重建、增强机体肿瘤免疫应答，抑制脑胶质瘤的复发和进展，从而有效地延长脑胶质瘤患者的生存时间。     

甲状腺癌中免疫活性细胞亚群的原位分析

 应用免疫组化ABC方法,我们对30例甲状腺癌和21例甲状腺良性病变组织中浸润的免疫活性细胞进行了单克隆抗体（Leu4、OKT₄、OKT₈、B₁、M718）的原位标记。结果显示甲状腺癌内浸润的单个核细胞（MNC）主要为T细胞和巨噬细胞及少量B细胞。OKT₄/OKT₈为1.35。M718⁺多核巨噬细胞在局部组织内存在为甲状腺癌的特征之一。相反,甲状腺良性病变内MNC量很少。本研究提示MNC和多核巨噬细胞的浸润与癌的类型及病人预后有关。     

卵巢癌患者CA125 表达和免疫状态关系研究

 目的 探讨卵巢癌患者血清CA125和机体免疫功能的关系及其临床意义。方法 采用流式细胞术检测患者外周血细胞CD3⁺、CD4⁺、NK⁺ (CD3^-／CD(16+56) ⁺)浓度细胞的百分率，采用酶联免疫法检测患者血清CA125的浓度。结果 卵巢癌患者血清CA125浓度显著高于正常对照组(P<0．01)：患者CD3⁺、CD⁺、和NK⁺细胞均显著低于正常对照组(P<0．05或P<0．01)。随着患者血清CA125浓度的增加，CD3⁺、CD4⁺、NK⁺细胞均逐渐降低，并呈显著的负相关(相关系数分别为r1=-0．959，P<0．01；r2=-0．923，P<0．05；r3=-0．912，P<0．05)。随着临床分期的增加，CA125浓度逐渐增加，CD3⁺、CD4⁺和NK⁺细胞则逐渐降低；伴肿瘤转移者的CA125浓度显著高于未转移者(P<0．01)，而CD3⁺、CD4⁺和NK⁺细胞却显著低于未转移者(P<0．05)。结论 卵巢癌能引起患者血清CA125表达率明显上升，而机体免疫功能显著下降。CA125的表达与患者免疫状态之间以及它们与临床生物学行为之间都有一定关系。     

低分化鼻咽癌细胞系单克隆株（4-2-H5）细胞膜电位研究

 从人低分化鼻咽癌细胞系（CNE-2Z）中分离出4-2-H₅单克隆细胞株，进行体外培养。应用玻璃微电极细胞内记录方法测量细胞膜电位。结果表明：与CNE-2Z相比，克隆抹细胞膜电位差异减小；随培养时间延长，膜电位负值减小，差异有非常显著意义（P<0.01）；培养液K⁺浓度提高，膜电位负值减小，差异有非常显著意义（P<0.01）；将培养液Na⁺提高20mmol/L，膜电位无明显改变。本结果提示：衰老变性的细胞膜电位负值减小，K⁺外流是形成H₅细胞静息电位的主要离子基础。     

体外培养DC-CIK细胞杀伤白血病细胞实验研究

目的:未缓解的急性白血病患者的外周血中存在一定比例的白血病细胞,能否诱导CIK细胞的增殖用于复发难治白血病的挽救治疗值得探讨。体外诱导培养缓解期及未缓解期急性白血病患者来源的DC-CIK细胞,比较其增殖能力,免疫表型及杀瘤活性的变化。方法:提取复发难治白血病患者和缓解期患者的研究对象的外周血单个核细胞,按常规方法诱导产生DC-CIK细胞,在培养过程中计算细胞增殖倍数,用流式细胞仪检测CD3CD8、CD3CD56双阳性率,并在细胞增殖期检测比较其对K562细胞及患者单个核细胞的杀伤活性。结果:缓解组和未缓解组来源的DC-CIK细胞均不断快速增殖,培养第15天时,缓解组CD3₊CD8₊和CD3₊CD56₊细胞分别占(87.5EeEe1.29)%,(63.8EeEe1.98)%,未缓解组分别占(88.6EeEe3.4)%,(66.8EeEe4.1)%,此时应用CCK-8法测得在效靶比为20:1时,缓解组对K562细胞的杀伤率为(42.64EeEe3.25)%,未缓解组为(57.49EeEe2.87)%;相同效靶比下,未缓解组对患者的单个核细胞的杀伤率为(67.29EeEe7.95)%。结论:应用未缓解患者的外周血单个核细胞,同样可以培养出DC-CIK细胞,具有与缓解组来源的DC-CIK细胞一致的高增殖活性和高CD3₊CD8₊、CD3₊CD56₊表达,一样对K562细胞杀伤活性较强,并对患者单个核细胞具有特异杀伤活性,未缓解患者来源的CIK细胞中未检测到白血病细胞残留,可以应用于难治白血病的挽救治疗。     

LAK细胞/IL-2联合放射免疫治疗晚期肿瘤的临床研究

 观察了72例接受不同方法治疗的晚期消化道恶性肿瘤患者愈后及γ显像情况,患者随机分为3组,第一组21例单独应用¹³¹I标记的抗结肠癌单克隆抗体CL₃(简称¹³¹I-CL₃)局部多点注射治疗;第二组33例接受LAK细胞/IL-2静脉注射治疗;第三组18例接受LAK细胞/IL-2联合¹³¹I-CL₃肿瘤局部多点注射治疗。发现:(1)LAK细胞/IL-2和¹³¹I-CL₃联合应用组,肿瘤局部核素标记抗体浓聚大于¹³¹I-CL₃组。(2)联合应用LAK细胞/IL-2及¹³¹I-CL₃治疗组的有效率(CR+PR,50%)明显高于¹³¹I-CL₃治疗组(238%)及LAK细胞/IL-2治疗组(121%)。说明LAK细胞/IL-2联合应用后可增强放免显像及放免治疗的效果。     

鼻咽癌组织与外周血CD4+CD25+调节性T细胞检测及临床意义

 目的 通过检测鼻咽癌患者肿瘤组织及外周血中CD4⁺T、CD8⁺T、CD4⁺CD25^-T、CD4⁺CD25⁺T细胞的频数,寻找客观、全面评价鼻咽癌患者免疫状态的临床指标。方法 采用流式细胞术检测40例初诊鼻咽癌患者及10例正常对照鼻咽部组织和外周血CD4⁺T、CD8⁺T、CD4⁺CD25^-T、CD4⁺CD25⁺T细胞比例。结果 鼻咽癌患者CD4⁺T细胞比例及CD4⁺/ CD8⁺T比值均低于对照组（P<0.05）,而CD8⁺T细胞两组间差异无统计学意义（P>0.05）,但是CD4⁺/ CD8⁺T比值在鼻咽癌组织与外周血间差异无统计学意义（P>0.05）。鼻咽癌组织及外周血中CD4⁺CD25⁺T细胞比例都高于对照组（P<0.05）,同时癌组织中该细胞比例远远高于外周血（P<0.05）。在鼻咽癌组织中CD4⁺CD25⁺T细胞与CD8+ T细胞、CD4⁺CD25^-T细胞呈负相关（r分别为-0.70、-0.675,P<0.05）,而在外周血中没有相关关系（P>0.05）。在不同T(原发肿瘤大小)组间,T4组的鼻咽癌组织中CD4⁺CD25⁺T细胞分别高于T1、T2、T3各组（P<0.05）,而在T1、T2、T3各组间差异无统计学意义（P>0.05）;鼻咽癌中CD4⁺CD25⁺T细胞比例与患者有无淋巴结转移并无关系（P>0.05）;鼻咽癌组织中Ⅲ+Ⅳ期组CD4⁺CD25⁺T细胞比例高于Ⅰ+Ⅱ期组（P<0.05）,而在外周血中两组间差异无统计学意义（P>0.05）。结论 CD4⁺CD25⁺T细胞与鼻咽癌病程进展无相关性,但是联合检测患者肿瘤组织及外周血中CD4⁺CD25⁺T细胞的频数并结合既往CD4⁺/ CD8⁺T比值会全面反应患者免疫状态,为临床治疗提供依据。     

氧化勒欓碱及双稠吡咯啶生物碱对肺癌A549细胞作用的研究

 氧化勒碱(Oxyavicine)和双稠吡咯啶生物碱(Pyrrolizidinealkaloids)是新近从植物中提取的抗癌药物, 本实验用以上二药作用于肺癌A₅₄₉细胞后, 观察了肺癌A₅₄₉细胞的生长曲线、分裂指数、摄取³H-胸腺嘧啶核苷合成DNA的能力以及癌细胞超微结构的变化。 结果表明:用药组肺癌A₅₄₉细胞生长曲线斜率下降；最大生长密度减少．分裂指数降低；合成DNA能力下降; 扫描电镜和透射电镜下癌细胞超微结构破坏。 实验结果提示:二药均能抑制肺癌A₅₄₉细胞的生长, 破坏其超微结构, 二者联合使用则具有协同作用。     

A study on the CD<Subscript>4</Subscript><Superscript>+</Superscript> CD<Subscript>25</Subscript><Superscript>+</Superscript> regulatory T cells in patients with gastrointestinal malignancies

Objectives Regulatory T cells play an active role in the maintenance of the immune system’s tolerance of both foreign and self antigens. Particularly, CD₄ ⁺ CD₂₅ ⁺ regulatory T cells participate in tumor immunity. The study provided further evidence on the involvement of CD₄ ⁺ CD₂₅ ⁺ regulatory T cells in immune system impairment in patients with gastrointestinal malignancies. Methods Using flow cytometry, CD₄ ⁺ CD₂₅ ⁺ regulatory T cells were analyzed in peripheral blood from 114 patients with gastrointestinal malignancies and 15 healthy controls. Results The prevalence of the CD₂₅ ⁺ subset in CD₄ ⁺ T cells was increased in patients with colorectal carcinoma compared with healthy controls. The phenotic characteristics of the CD₄ ⁺ CD₂₅ ⁺ T cells in patient with malignancies were low expression of CD₄₅ RA and no expression of CD₆₉. Our results indicated that when compared with healthy control, the proportions of CD₄ ⁺ CD₂₅ ⁺ T cells in the peripheral blood of patients with colorectal, gastric, and esophageal carcinoma were significantly higher (P < 0.05) in colorectal carcinoma (22.11 ± 9.65%), gastric carcinoma (17.74 ± 4.24%), and esophageal carcinoma (24.37 ± 4.82)%, respectively. Further analysis on the proportion of CD₄ ⁺ CD₂₅ ⁺ T cells revealed that those patients with gastrointestinal malignancies in stages IV were higher than those of in stage I–III, though no significant difference was observed (P > 0.05). However, the proportion of CD₄ ⁺ CD₂₅ ⁺ T cells in the patients with relapse gastric carcinoma (23.32 ± 4.98%) was significantly higher than that of patients with primary gastric carcinoma (P < 0.01). Conclusions The increased CD₄ ⁺ CD₂₅ ⁺ T cells in patients with gastrointestinal malignancies may be related to immunosuppression and tumor progression. This suggests that elimination or reduction of CD₄ ⁺ CD₂₅ ⁺ regulatory T cells can improve effective tumor immunity for immunotherapy.     

Study of Multi-directional Derivation of Cord Blood Mononuclear Cells and Observation of Killing Activity to MGC-803 Gastric Cancer Cell Strain In Vitro

Objective： To study multi-directional derivation of cord blood mononuclear cells to CD3AK, LAK and CIK cells as well as changes of killing activity to gastric cancer cell strain in vitro. Methods： CD3mAb and IL-2 were used to induce CD3AK cells, and IL-2 was used to induce LAK cells; IFN-γ was used in the beginning, then IL-1, CD3mAb and IL-2 were used to induce CIK cells after 24 h for observing amplification and analyzing their relationship. The phenotypes of the cultured CIK cells were analyzed by flow cytometry. Subsequently, by using MGC-803 gastric cancer cell strain as target cells, the killing activity of CD3AK, LAK and CIK cells was evaluated by using MTT method. Results： The amplification activity of CD3AK and CIK cells was all far higher than LAK cells （P〈0.05）. The amplification activity had no obvious difference between CIK cells and CD3AK cells at prophase, but that was far higher in CIK cells than CD3AK cells at about 20^th day （P〈0.05）. The flow cytometry revealed that the amount of CD3^＋ CD56^＋ cells, major effector cells after CIK cells being cultured was significantly increased （P〈0.05）, moreover, the amount of CD8^＋ cells was significantly increased as well （P〈0.05）. The killing activities of CD3AK and CIK cells to the MGC-803 gastric cancer cell strain were all significantly higher than LAK cells, while the killing activity of CIK cells was stronger than CD3AK cells （P〈0.05）. Conclusion： CIK cells have stronger amplification activity and killing activity, and can be taken as more effective killing cells applied to the tumor adoptive immunotherapy.     

Changing Trends of HIV/AIDS in Otorhinolaryngology with CD<Subscript>4</Subscript><Superscript>+</Superscript> Count Correlation

Human immunodeficiency virus (HIV) affects the vital cells of the immune system eventually leading to a fall in the cell mediated immunity. As the disease progresses CD₄ ⁺ (cluster of differentiation4) cells reduce, therefore is a good indicator of the ongoing disease process [1]. HIV infection has myriads of disease presentation; the aim of our study was to correlate the otorhinolaryngological manifestations with the CD₄ ⁺ counts. A clinical study, of 100 HIV positive patients was done from 2008 to 2011. A clinical evaluation revealed 76 % incidence of otorhinolaryngological findings. Oropharyngeal manifestations were the commonest, seen in 48 %, predominantly oropharyngeal candidiasis. Neck nodes were found in 20 % of the patients. 31 % had otological manifestations of which retracted tympanic membrane (eustachian tube dysfunction) was the commonest. 18 % had nasal symptoms of which rhinosinusitis was the commonest being 14 %. The mean CD₄ ⁺ count was below 200 in patients who presented with oropharyngeal candidiasis, otitis externa and epistaxis. With the use and availability of HAART (Highly active antiretroviral therapy) more and more patients with higher CD₄ ⁺ count are presenting with a different spectrum of more subtle disease manifestations, with lower incidence of the classical diseases like candidiasis. A routine otorhinolaryngological evaluation at every visit with high index of suspicion can help in better disease control and give a better quality of life.     

CD4+ and CD8+ T cells have opposing roles in breast cancer progression and outcome

The Cancer Immunoediting concept has provided critical insights suggesting dual functions of immune system during the cancer initiation and development. However, the dynamics and roles of CD4⁺ and CD8⁺ T cells in the pathogenesis of breast cancer remain unclear. Here we utilized two murine breast cancer models (4T1 and E0771) and demonstrated that both CD4⁺ and CD8⁺ T cells were increased and involved in immune responses, but with distinct dynamic trends in breast cancer development. In addition to cell number increases, CD4⁺ T cells changed their dominant subsets from Th1 in the early stages to Treg and Th17 cells in the late stages of the cancer progression. We also analyzed CD4⁺ and CD8⁺ T cell infiltration in primary breast cancer tissues from cancer patients. We observed that CD8⁺ T cells are the key effector cell population mediating effective anti-tumor immunity resulting in better clinical outcomes. In contrast, intra-tumoral CD4⁺ T cells have negative prognostic effects on breast cancer patient outcomes. These studies indicate that CD4⁺ and CD8⁺ T cells have opposing roles in breast cancer progression and outcomes, which provides new insights relevant for the development of effective cancer immunotherapeutic approaches.     

宫颈癌患者外周血T淋巴细胞亚群和NK细胞数量与临床分期的相关性分析

目的 探讨宫颈癌患者外周血T淋巴细胞亚群和NK细胞数量的变化及其与宫颈癌分期的相关性.方法 收集2010年6月-2011年6月期间在沈阳医学院奉天医院妇科治疗的146例宫颈癌患者及同期在我院进行体检的50例健康女性(对照组),宫颈癌患者根据临床分期分为0期、Ⅰ期、Ⅱ期、Ⅲ期、Ⅳ期5组.采用免疫荧光法和流式细胞仪测定各组患者外周血T淋巴细胞亚群和NK细胞数量.结果 宫颈癌患者CD3+,CD3+ CD4+,NK细胞数量及CD3+ CD4+/CD3+ CD8+比值均低于对照组,且随分期增加而逐渐降低;而CD3+ CD8+细胞数量高于对照组,且随分期增加而逐渐增高.CD3+、CD3+CD4+、NK细胞数量及CD3+ CD4+/CD3+ CD8+细胞比值与宫颈癌临床分期呈负相关(P＜0.01);CD3+ CD8+细胞数量与宫颈癌分期呈正相关(P＜0.01).结论 宫颈癌患者细胞免疫功能低下,且临床分期越晚,免疫功能越低,检测T淋巴细胞亚群、NK细胞可用于宫颈癌患者的免疫监测.     

Immune landscape of vulvar cancer patients treated with surgery and adjuvant radiotherapy revealed restricted T cell functionality and increased IL-17 expression associated with cancer relapse

For vulvar cancers, radiotherapy is targeting cancer cells, but also affects the host immune system. As this may affect treatment outcome, in this prospective study, we characterized the individual T cell immune milieu induced by surgery and adjuvant radio +/− chemotherapy (aRT) systemically in the blood of vulvar cancer patients and found increased frequencies of Interleukin (IL)-17-producing CD4⁺ and CD8⁺ T cells after aRT while frequencies of Th1 and perforin-producing CD8⁺ killer cells were strongly diminished. Phenotypic characterization revealed enhanced expression of the ectonucleotidase CD39 on Th17 and Tc17 cells as well as CD8⁺ perforin⁺ cells after aRT. Furthermore, the aRT cohort exhibited increased proportions of Programmed Cell Death Protein (PD-1) expressing cells among Th1 and CD8⁺ perforin⁺ cells, but not among Th17 and Tc17 cells. High post-therapeutic levels of Th17 and Tc17 cells and low proportions of Th1 and CD8⁺ perforin⁺ cells expressing PD-1 was associated with reduced recurrence free survival on follow-up. In conclusion, our study defines individual therapy-induced changes in the cellular immune milieu of patients and their association with cancer relapse. Our results may help to explain differences in the individual courses of disease of vulvar cancer patients and suggest PD-1 and IL-17 as targets for immunotherapy in vulvar cancer.     

Dynamic changes in immune cell profile in head and neck squamous cell carcinoma: Immunomodulatory effects of chemotherapy

Tumor cells have evolved sophisticated means of escape from the host immune system. To date, several important immunological phenomena have been revealed in peripheral blood as well as within tumors. In the present study, we first investigated the proportion and activation status of peripheral immune regulatory cells and CD8⁺ T‐cell subsets in patients with head and neck squamous cell carcinoma (HNSCC) using a multicolor flow cytometer, and then evaluated how therapy with docetaxel, cisplatin, and 5‐fluorouracil modulated the immune cell profile in peripheral blood. The proportion of naïve T cells was lower and that of effector memory T cells (T_EM) was higher in HNSCC patients than in healthy donors. Moreover, the proportions of activated T_EM cells and effector T cells (T_EFF) were dramatically increased in patients with advanced stage disease. The proportion of regulatory T cells and CD14⁺HLA‐DR^? myeloid‐derived suppressor cells was elevated in HNSCC patients. Of note, after therapy, in addition to the transient reduction in immune regulatory cells, decreases in central memory T cells and increases in T_EFF cells were observed among CD8⁺ T‐cell subsets, suggesting differentiation from central memory T cells into T_EFF cells. Our results suggested that, despite the immunosuppressive status in HNSCC patients, tumor‐specific immune responses mediated by CD8⁺ T cells might be induced and maintained. Moreover, chemotherapy can trigger not only a transient reduction in immune regulatory cells but also further activation of CD8⁺ T cells.     

Analysis of radiotherapy-induced alteration of CD8+ T cells and PD-L1 expression in patients with uterine cervical squamous cell carcinoma

Radiotherapy induces an immune response in the cancer microenvironment that may influence clinical outcome. The present study aimed to analyse the alteration of CD8⁺ T-cell infiltration and programmed death-ligand 1 (PD-L1) expression following radiotherapy in clinical samples from patients with uterine cervical squamous cell carcinoma. Additionally, the current study sought to analyse the association between these immune responses and clinical outcomes. A total of 75 patients who received either definitive chemoradiotherapy or radiotherapy were retrospectively analyzed. CD8⁺ T-cell infiltration and PD-L1 expression were determined by immunohistochemistry using biopsy specimens before radiotherapy (pre-RT) and after 10 Gy radiotherapy (post-10 Gy). The PD-L1⁺ rate was significantly increased from 5% (4/75) pre-RT to 52% (39/75) post-10 Gy (P<0.01). Despite this increase in the PD-L1⁺ rate post-10 Gy, there was no significant association between both pre-RT and post-10 Gy and overall survival (OS), locoregional control (LC) and progression-free survival (PFS). On the other hand, the CD8⁺ T-cell infiltration density was significantly decreased for all patients (median, 23.1% pre-RT vs. 16.9% post-10 Gy; P=0.038); however, this tended to increase in patients treated with radiotherapy alone (median, 17.7% pre-RT vs. 24.0% post-10 Gy; P=0.400). Notably, patients with high CD8⁺ T-cell infiltration either pre-RT or post-10 Gy exhibited positive associations with OS, LC and PFS. Thus, the present analysis suggested that CD8⁺ T-cell infiltration may be a prognostic biomarker for patients with cervical cancer receiving radiotherapy. Furthermore, immune checkpoint inhibitors may be effective in patients who have received radiotherapy, since radiotherapy upregulated PD-L1 expression in cervical cancer specimens.     

NK- and T-cell subsets in malignant mesothelioma patients: Baseline pattern and changes in the context of anti-CTLA-4 therapy

Malignant mesothelioma (MM) is a highly aggressive form of cancer with limited treatment options. Although the role of NK cells has been studied in many solid tumors, the pattern of NK-cell subsets and their recognition of mesothelioma cells remain to be explored. We used RNA expression data of MM biopsies derived from the cancer genome atlas to evaluate the immune cell infiltrates. We characterized the phenotype of circulating NK and T cells of 27 MM patients before and after treatment with an anti-CTLA-4 antibody (tremelimumab). These immune cell profiles were compared to healthy controls. The RNA expression data of the MM biopsies indicated the presence of NK cells in a subgroup of patients. We demonstrated that NK cells recognize MM cell lines and that IL-15 stimulation improved NK cell-mediated lysis in vitro. Using multivariate projection models, we found that MM patients had a perturbed ratio of CD56^bright and CD56^dim NK subsets and increased serum concentrations of the cytokines IL-10, IL-8 and TNF-α. After tremelimumab treatment, the ratio between the CD56^bright and CD56^dim subsets shifted back towards physiological levels. Furthermore, the improved overall survival was correlated with low TIM-3⁺CD8⁺ T-cell frequency, high DNAM-1⁺CD56^dim NK-cell frequency and high expression levels of NKp46 on the CD56^dim NK cells before and after immune checkpoint blockade. Together, our observations suggest that NK cells infiltrate MM and that they can recognize and kill mesothelioma cells. The disease is associated with distinct lymphocytes patterns, some of which correlate with prognosis or are affected by treatment with tremelimumab.