OBJECTIVE: To investigate the clinical characteristics and treatment of relapsed CD5+ diffuse large B-cell lymphoma (DLBCL).
METHODS: The data of a patient with CD5+ DLBCL was collected, and its clinical characteristics and treatment outcome were analyzed.
RESULTS: The patient developed hemophagocytic syndrome and achieved complete remission (CR) after 6 cycles of R-ECHOP chemotherapy, then relapsed. After 2 cycles of PD-1 inhibitor combined with lenalidomide treatment, the patient achieved CR again accompanied by a decrease of interleukin (IL)-10 expression level. After a total of 15 cycles of chemotherapy, the patient remained in CR for 24 months, and the level of IL-10 remained in the normal range.
CONCLUSIONS: PD-1 inhibitor combined with lenalidomide regimen may be a new treatment for relapsed CD5+ DLBCL.
UNASSIGNED: PD-1抑制剂联合来那度胺治疗复发CD5+弥漫大B细胞淋巴瘤临床分析.
UNASSIGNED: 探讨复发CD5+弥漫大B细胞淋巴瘤的临床特征及治疗方法。.
UNASSIGNED: 收集1例CD5+弥漫大B细胞淋巴瘤患者的资料，分析其临床特征、治疗转归。.
UNASSIGNED: 患者合并噬血细胞综合征，经6周期R-ECHOP方案化疗达完全缓解后复发，给予PD-1抑制剂联合来那度胺治疗2周期再次达完全缓解，伴随着白介素-10表达水平下降。患者前后共化疗15个周期，病情持续处于完全缓解状态，缓解时间达24个月，白介素-10的水平持续处于正常范围。.
UNASSIGNED: PD-1抑制剂联合来那度胺方案有望成为治疗复发CD5+弥漫大B细胞淋巴瘤新方案。.

Most patients treated with US Food and Drug Administration (FDA)-approved chimeric antigen receptor (CAR) T cells eventually experience disease progression. Furthermore, CAR T cells have not been curative against solid cancers and several hematological malignancies such as T cell lymphomas, which have very poor prognoses. One of the main barriers to the clinical success of adoptive T cell immunotherapies is CAR T cell dysfunction and lack of expansion and/or persistence after infusion. In this study, we found that CD5 inhibits CAR T cell activation and that knockout (KO) of CD5 using CRISPR-Cas9 enhances the antitumor effect of CAR T cells in multiple hematological and solid cancer models. Mechanistically, CD5 KO drives increased T cell effector function with enhanced cytotoxicity, in vivo expansion, and persistence, without apparent toxicity in preclinical models. These findings indicate that CD5 is a critical inhibitor of T cell function and a potential clinical target for enhancing T cell therapies.

Chimeric antigen receptor T cells (CART) targeting lymphocyte antigens can induce T cell fratricide and require additional engineering to mitigate self-damage. We demonstrate that the expression of a chimeric antigen receptor (CAR) targeting CD5, a prominent pan-T cell antigen, induces rapid internalization and complete loss of the CD5 protein on T cells, protecting them from self-targeting. Notably, exposure of healthy and malignant T cells to CD5.CART cells induces similar internalization of CD5 on target cells, transiently shielding them from cytotoxicity. However, this protection is short-lived, as sustained activity of CD5.CART cells in patients with T cell malignancies results in full ablation of CD5+ T cells while sparing healthy T cells naturally lacking CD5. These results indicate that continuous downmodulation of the target antigen in CD5.CART cells produces effective fratricide resistance without undermining their on-target cytotoxicity.

OBJECTIVE: To analyze the clinical characteristics and prognosis of patients with CD5+ diffuse large B-cell lymphoma (DLBCL).
METHODS: The clinical data of 161 newly treated DLBCL patients in Gansu Provincial Hospital from January 2013 to January 2020 were retrospectively analyzed. According to CD5 expression, the patients were divided into CD5+ group and CD5- group. The clinical characteristics and prognosis of the two groups were statistically analyzed.
RESULTS: The median age of patients in CD5+ group was 62 years, which was higher than 56 years in CD5- group (P =0.048). The proportion of women in CD5+ group was 62.96%, which was significantly higher than 41.79% in CD5- group (P =0.043). The proportion of patients with IPI score > 2 in CD5+ group was 62.96%, which was higher than 40.30% in CD5- group (P =0.031). Survival analysis showed that the median overall survival and progression-free survival time of patients in CD5+ group were 27(3-77) and 31(3-76) months, respectively, which were both shorter than 30(5-84) and 32.5(4-83) months in CD5- group (P =0.047, P =0.026). Univariate analysis showed that advanced age, positive CD5 expression, triple or double hit at initial diagnosis, high IPI score and no use of rituximab during chemotherapy were risk factors for the prognosis of DLBCL patients. Further Cox multivariate regression analysis showed that these factors were also independent risk factors except for advanced age.
CONCLUSIONS: CD5+ DLBCL patients have a worse prognosis than CD5- DLBCL patients. Such patients are more common in females, with advanced age and high IPI score, which is a special subtype of DLBCL.
UNASSIGNED: CD5阳性弥漫大B细胞淋巴瘤患者的临床特征及预后分析.
UNASSIGNED: 分析CD5阳性弥漫大B细胞淋巴瘤（DLBCL）患者的临床特征及预后影响因素。.
UNASSIGNED: 回顾性分析自2013年1月至2020年1月甘肃省人民医院就诊的161例初治DLBCL患者的临床资料，根据CD5表达情况，将患者分为CD5+组和CD5-组，并对两组患者的临床特征、预后生存进行统计学分析。.
UNASSIGNED: 临床特征分析结果显示，CD5+组患者的中位年龄为62岁，高于CD5-组的56岁（P =0.048）；CD5+组患者女性占比为62.96%，明显高于CD5-组的41.79%（P =0.043）；CD5+组IPI评分>2分患者的比例为62.96%，高于CD5-组患者的40.30%（P =0.031）。生存分析结果显示，CD5+组的中位总生存期和无进展生存期分别为27（3-77）个月、31（3-76）个月，均短于CD5-组的30（5-84）个月、32.5（4-83）个月，比较差异有统计学意义（P =0.047，P =0.026）。单因素分析结果显示，高龄、CD5表达为阳性、初诊时存在三打击或双打击、较高的IPI评分及化疗过程中未使用利妥昔单抗是影响DLBCL患者预后的危险因素，进一步行Cox多因素回归分析结果显示，除高龄外以上均是独立危险因素。.
UNASSIGNED: CD5+ DLBCL患者预后相对CD5- 患者更差，此类患者多见于女性，高龄、IPI评分高，是一类特殊的DLBCL亚型。.

The Bruton\'s tyrosine kinase (BTK) inhibitor ibrutinib represents an effective strategy for treatment of chronic lymphocytic leukemia (CLL), nevertheless about 30% of patients eventually undergo disease progression. Here we investigated by flow cytometry the long-term modulation of the CLL CXCR4dim/CD5bright proliferative fraction (PF), its correlation with therapeutic outcome and emergence of ibrutinib resistance. By longitudinal tracking, the PF, initially suppressed by ibrutinib, reappeared upon early disease progression, without association with lymphocyte count or serum beta-2-microglobulin. Somatic mutations of BTK/PLCG2, detected in 57% of progressing cases, were significantly enriched in PF with a 3-fold greater allele frequency than the non-PF fraction, suggesting a BTK/PLCG2-mutated reservoir resident within the proliferative compartments. PF increase was also present in BTK/PLCG2-unmutated cases at progression, indicating that PF evaluation could represent a marker of CLL progression under ibrutinib. Furthermore, we evidence different transcriptomic profiles of PF at progression in cases with or without BTK/PLCG2 mutations, suggestive of a reactivation of B-cell receptor signaling or the emergence of bypass signaling through MYC and/or Toll-Like-Receptor-9. Clinically, longitudinal monitoring of the CXCR4dim/CD5bright PF by flow cytometry may provide a simple tool helping to intercept CLL progression under ibrutinib therapy.

暂无摘要。

目的： 探讨套细胞淋巴瘤（MCL）浸润骨髓的病理组织学特征及与预后的相关性。 方法： 回顾性分析江苏省人民医院2008年1月至2021年12月95例MCL患者的临床特征、病理特点及预后因素。 结果： MCL典型患者，男性71例，女性24例，镜下观察形态为一致的小淋巴样细胞，核为圆形或不规则，母细胞类型类似于淋巴母细胞，骨髓侵犯以弥漫性最为多见（35例），其次为结节性（31例）、局灶性（19例）、间质浸润（10例）。并有25例表现为多种生长方式合并出现，呈混合型浸润。免疫表型：表达CD5、CD20、CD79a、PAX5等B淋巴细胞标志物，其特征性表达为cyclin D1胞核阳性。在少数Cyclin D1 阴性的患者中可见SOX11强表达。 结论： MCL较易发生骨髓受累，对MCL的骨髓浸润模式及浸润程度有必要细分亚型，从而为临床治疗及预后判断提供参考。.

Cyclin D1 protein-positive diffuse large B cell lymphoma (DLBCL) has an immunophenotype of CD5(-) cyclin D1(+) SOX11(-), and most cases lack a CCND1 rearrangement and have a gene expression profile of DLBCL. Rarely, cyclin D1 protein-positive DLBCL harbors a CCND1 rearrangement, and some genetic copy number features typical of mantle cell lymphoma (MCL) have been detected. Since gene expression studies have not been performed, whether such CCND1-rearranged cases represent cyclin D1 protein-positive DLBCL or CD5/SOX11 double-negative pleomorphic MCL remains unclear. To date, no cases of CD5/SOX11 double-negative MCL have been reported. In this study, we collected eight cases initially diagnosed as cyclin D1 protein-positive DLBCL, including four with a CCND1 rearrangement and four without. Immunohistochemically, all four CCND1-rearranged cases had >50% of tumor cells positive for cyclin D1 protein, whereas only one (25%) non-rearranged case had >50% positive tumor cells. Analysis of genome-wide copy number, mutational, and gene expression profiles revealed that CCND1-rearranged cases were similar to MCL, whereas CCND1-non-rearranged cases resembled DLBCL. Despite the SOX11 negativity by immunohistochemistry, CCND1-rearranged cases had a notable trend (P = 0.064) of higher SOX11 mRNA levels compared to non-rearranged cases. Here, we show for the first time that CCND1 rearrangement could be useful for identifying CD5/SOX11 double-negative pleomorphic MCL in cases diagnosed as cyclin D1 protein-positive DLBCL. Cases with >50% cyclin D1 protein-positive tumor cells immunohistochemically and higher SOX11 mRNA levels are more likely to have a CCND1 rearrangement, and fluorescence in situ hybridization can be used to detect the rearrangement.

Objective: To analyze the clinicopathological features of salivary carcinoma showing thymus-like differentiation(CASTLE). Methods: Cases diagnosed with salivary CASTLE from January 2020 to December 2023 were collected and selected from the Department of Oral Pathology, Shanghai Ninth People\'s Hospital, Shanghai Jiao Tong University School of Medicine. A total of 7 cases of salivary CASTLE were identified. All the cases originated from parotid. There were 3 males and 4 females. The patients\' age range was 11-70 years.The clinical, microscopic, immunohistochemical and prognostic features of these cases were analyzed. Results: The duration of disease ranged from 1 month to 1 year, and 1 patient had facial numbness and 1 with swelling sensation occasionally. Radiographically, 4 cases showed malignant signs. Microscopically, 4 cases involved in parotid gland, and all the tumors had different degrees of lymphoid tissue background. The tumor cells arranged in nests, 5 cases with lymphoepithelial carcinoma-like and 2 cases with squamous cell carcinoma morphology. The tumor cells expressed CD5 and CD117 proteins diffusely in lymphoepithelial carcinoma-like cases. However, the tumor cells expressed CD5 diffusely and CD117 focally in cases with squamous cell carcinoma morphology. All the cases had no Epstein-Barr virus infection. Among the 6 patients with follow-up information, all of them underwent postoperative radiotherapy, and none of them had local recurrence and lymph node metastasis. Conclusions: Salivary CASTLE is a rare tumor, it should be distinguished from lymphoepithelial carcinoma and squamous cell carcinoma. The patients often have better prognosis and CD5 protein expression has a valuable role in the differential diagnosis.
目的： 分析唾液腺伴胸腺样分化的癌（CASTLE）临床病理特点。 方法： 收集并筛选上海交通大学医学院附属第九人民医院口腔病理科2020年1月至2023年12月期间满足唾液腺CASTLE诊断的病例。共收集7例患者，其中男性3例，女性4例，年龄11~70岁。分析患者的临床表现、镜下表现、免疫组化、预后等特点。 结果： 7例唾液腺CASTLE均位于腮腺；病史1个月~1年，1例患者伴有面部麻木，1例偶有肿胀感；影像学上，4例考虑恶性肿瘤或恶性肿瘤待排。显微镜下，4例肿瘤累及周围腺体组织，所有肿瘤具有多少不一的淋巴组织背景，肿瘤细胞排列呈巢状，其中5例呈淋巴上皮癌样，2例呈鳞状细胞癌图像；淋巴上皮癌样肿瘤细胞除表达CD5外，还可表达CD117，呈鳞状细胞癌图像的病例局灶或部分表达CD117；所有病例均无EB病毒感染。6例有随访信息的患者均行术后放疗，均未见肿瘤复发及转移。 结论： 唾液腺CASTLE是一种少见的肿瘤，需与淋巴上皮癌和鳞状细胞癌鉴别，患者预后尚好，CD5在鉴别诊断中具有较大价值。.

The function of CD5 protein in T cells is well documented, but regulation of its surface-level expression has yet to be fully understood. However, variation in its surface expression is associated with various immunopathological conditions and haematological malignancies. Briefly, expression of an alternate exon E1B of a human endogenous retroviruses (HERV) origin directly downregulates the conventional transcript variant (E1A), as its expression leads to the retention of the resultant protein at the intracellular level (cCD5). A separate promoter governs the expression of E1B and may be influenced by different transcription factors. Hence, we performed in silico transcription factor binding site (TFBS) analysis of the 3 kb upstream region from TSS of exon E1B and found five putative DREs (Dioxin Response elements) with good similarity scores. Further, we observed the upregulation in E1B expression after the exposure of BaP (a dioxin) and the reduction of E1A expression and their respective protein, i.e. sCD5 and cCD5. The binding of AHR at the predicted DRE sites was confirmed by ChIP qPCR and AHR specific inhibitor and gene silencing studies suggested the involvement of AHR in exonal switch. This study indicates that the polycyclic aromatic hydrocarbon decreases the sCD5 expression by upregulating alternative exon expression, which may adversely affect the overall T cell functions.