{"title":"Thymus transplantation as immunotherapy for the enhancement and/or correction of T cell function.","authors":"Naoki Hosaka","doi":"10.1007/s00795-024-00394-z","DOIUrl":"10.1007/s00795-024-00394-z","url":null,"abstract":"<p><p>The thymus is where T cells, among the most important immune cells involved in biological defense and homeostasis, are produced and developed. The thymus plays an important role in the defense against infection and cancer as well as the prevention of autoimmune diseases. However, the thymus gland atrophies with age, which might have pathological functions, and in some circumstances, there is a congenital defect in the thymus. These can be the cause of many diseases related to the dysregulation of T cell functions. Thus, the enhancement and/or normalization of thymic function may lead to protection against and treatment of a wide variety of diseases. Therefore, thymus transplantation is considered a strong candidate for permanent treatment. The status and issues related to thymus transplantation for possible immunotherapy are discussed although it is still at an early stage of development.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"155-160"},"PeriodicalIF":1.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141457960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Usage of nivolumab and ipilimumab for recurrent or advanced malignant vaginal melanoma: a two-case series.","authors":"Kota Konishi, Mamiko Okamoto, Ryuichi Tokumitsu, Mitsutake Yano, Kaei Nasu, Eiji Kobayashi","doi":"10.1007/s00795-023-00377-6","DOIUrl":"10.1007/s00795-023-00377-6","url":null,"abstract":"<p><p>Immune checkpoint inhibitors help treat malignant melanoma, but show limited use in treating malignant vaginal melanoma, an aggressive, rare gynecological malignancy. We identified two patients treated with ipilimumab and nivolumab for vaginal melanoma; both were immunonegative for programmed cell death-ligand 1 and wild-type BRAF. Case 1, a 56-year-old female who underwent radical surgery for stage 1 malignant vaginal melanoma, experienced recurrence 15 months postoperatively. She briefly responded to ipilimumab and nivolumab combination therapy before showing disease progression. Tumor shrinkage occurred with nivolumab and local radiotherapy and, 45 months postoperatively, she survives with the melanoma. Case 2, a 50-year-old female, presented with a 4-cm blackish polypoid vaginal tumor with metastatic pelvic lymph nodes. She received ipilimumab and nivolumab combination therapy for stage III unresectable malignant vaginal melanoma. The vaginal tumor shrank after the third course of treatment, and the lymphadenopathy disappeared. The patient underwent radical surgery and is currently disease-free, using nivolumab for maintenance therapy. Both patients had immune-related adverse events coinciding with periods of high therapeutic efficacy of immune checkpoint inhibitors. Neoadjuvant therapy with immune checkpoint inhibitors and radiotherapy for immune checkpoint inhibitor resensitization may effectively treat advanced or recurrent vaginal melanoma.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"83-90"},"PeriodicalIF":1.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11128387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hong Wu, Yoshihiko Fujioka, Shoichi Sakaguchi, Youichi Suzuki, Takashi Nakano
{"title":"Morphological analysis for two types of viral particles in vacuoles of SARS-CoV-2-infected cells.","authors":"Hong Wu, Yoshihiko Fujioka, Shoichi Sakaguchi, Youichi Suzuki, Takashi Nakano","doi":"10.1007/s00795-024-00381-4","DOIUrl":"10.1007/s00795-024-00381-4","url":null,"abstract":"<p><p>In this study, we analyzed the morphological structure of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human cells. We identified the two types of viral particles present within the vacuoles of infected cells. Using transmission electron microscopy, we observed that SARS-CoV-2 particles exhibited both low- and high-electron-density structures, which was further confirmed through three-dimensional reconstruction using electron tomography. The budding of these particles was exclusively observed within these vacuoles. Intriguingly, viral particles with low-electron-density structures were confined to vacuoles, whereas those with high-electron-density structures were found in vacuoles and on the cell membrane surface of infected cells. Notably, high-electron-density particles found within vacuoles exhibited the same morphology as those outside the infected cells. This observation suggests that the two types of viral particles identified in this study had different maturation status. Our findings provide valuable insights into the molecular details of SARS-CoV-2 particles, contributing to our understanding of the virus.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"124-135"},"PeriodicalIF":1.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Characteristics of peripheral blood mononuclear cells and potential related molecular mechanisms in patients with autoimmune hepatitis: a single-cell RNA sequencing analysis.","authors":"Kazumichi Abe, Naoto Abe, Tatsuro Sugaya, Yosuke Takahata, Masashi Fujita, Manabu Hayashi, Atsushi Takahashi, Hiromasa Ohira","doi":"10.1007/s00795-024-00380-5","DOIUrl":"10.1007/s00795-024-00380-5","url":null,"abstract":"<p><p>Autoimmune hepatitis (AIH) is an immune disorder characterized by hypergammaglobulinemia, autoantibodies, and chronic active hepatitis on liver histology. However, immune cell population characteristics in AIH patients remain poorly understood. This study was designed to analyze peripheral blood mononuclear cell (PBMC) characteristics in AIH through single-cell RNA sequencing (scRNA-seq) and explore potential AIH-related molecular mechanisms. We generated 3690 and 3511 single-cell transcriptomes of PBMCs pooled from 4 healthy controls (HCs) and 4 AIH patients, respectively, by scRNA-seq. These pooled PBMC transcriptomes were used for cell cluster identification and differentially expressed gene (DEG) identification. GO functional enrichment analysis was performed on the DEGs to determine the most active AIH immune cell biological functions. Although the PCA-based uniform manifold approximation and projection (UMAP) algorithm was used to cluster cells with similar expression patterns in the two samples, 87 up- and 12 downregulated DEGs were retained in monocytes and 101 up- and 15 downregulated DEGs were retained in NK cells from AIH PBMCs. Moreover, enriched GO terms in the PBMC-derived monocyte and NK cell clusters were related mainly to antigen processing and presentation, IFN-γ-mediated signaling, and neutrophil degranulation and activation. These potential molecular mechanisms may be important targets for AIH treatment.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"110-123"},"PeriodicalIF":1.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genetic and histological analysis intraplacental choriocarcinoma: a case report.","authors":"Natsuko Takano, Masashi Takamura, Yosuke Mizuno, Yumi Mizuno, Shunsuke Tamaru, Kohei Nakamura, Hiroaki Soma, Takeshi Kajihara","doi":"10.1007/s00795-024-00382-3","DOIUrl":"10.1007/s00795-024-00382-3","url":null,"abstract":"<p><p>We report on single case of intraplacental choriocarcinoma (IC) coexisting with feto-maternal hemorrhage from our hospital, a rare malignant tumor that occurs in the chorionic villous trophoblast. To investigate genetic and epigenetic changes to the carcinogenesis of IC, we employed cancer gene panel analysis and whole methylation analysis from a recent case of IC. By Short Tandem Repeats analysis, we confirmed that the tumor of present IC was derived from concurrent normal chorionic villous trophoblast cells. No mutation was found in 145 cancer-related genes. Meanwhile, amplification in MDM2 gene was observed. Furthermore, we observed deferentially methylated CpG sites between tumor and surrounding normal placenta in present IC case. These observations suggest that IC might be arisen as a result of aberrations of methylation rather than of DNA mutations. Further studies are needed to clarify association between aberrant methylation and choriocarcinogenesis.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"147-154"},"PeriodicalIF":1.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11128402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"IL-32 production from lung adenocarcinoma cells is potentially involved in immunosuppressive microenvironment.","authors":"Shukang Zhao, Lianbo Li, Yoshihiro Komohara, Eri Matsubara, Yusuke Shinchi, Ahmad Adawy, Hiromu Yano, Cheng Pan, Yukio Fujiwara, Koei Ikeda, Shinya Suzu, Taizo Hibi, Makoto Suzuki","doi":"10.1007/s00795-023-00378-5","DOIUrl":"10.1007/s00795-023-00378-5","url":null,"abstract":"<p><p>Interleukin 32 (IL-32) is a proinflammatory cytokine secreted from several kinds of cancer cells. In the present study, we investigated the significance of IL-32 in lung adenocarcinoma by immunohistochemistry and bioinformatics analysis. IL-32 was positive in cancer cells of 21 cases (9.2%) of total 228 cases. Increased IL-32 gene expression was linked to worse clinical course in TCGA analysis, however, IL-32 expression in immunohistochemistry was not associated to clinical course in our cohort. It was also found that high IL-32 expression was seen in cases with increased lymphocyte infiltration. In vitro studies indicated that IFN-γ induced gene expression of IL-32 and PD1-ligands in lung adenocarcinoma cell lines. IL-32, especially IL-32β, also induced overexpression of PD1-ligands in human monocyte-derived macrophages. Additionally, Cancer-cell-derived IL-32 was elevated by stimulation with anticancer agents. In conclusion, IL-32 potentially induced by inflammatory conditions and anticancer therapy and contribute to immune escape of cancer cells via development the immunosuppressive microenvironment. IL-32 might be a target molecule for anti-cancer therapy.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"91-100"},"PeriodicalIF":1.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139692240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marya Obeidat, Wisam Algargaz, Marwa Barukba, Khaldon Bodoor, Issa Mohamad, Farid Barakat, Samir Al Bashir
{"title":"Clinical and molecular characteristics of Jordanian oropharyngeal cancer patients according to P16 expression: a retrospective study and a report of a novel biomarker.","authors":"Marya Obeidat, Wisam Algargaz, Marwa Barukba, Khaldon Bodoor, Issa Mohamad, Farid Barakat, Samir Al Bashir","doi":"10.1007/s00795-024-00383-2","DOIUrl":"10.1007/s00795-024-00383-2","url":null,"abstract":"<p><p>The purpose of this study was to assess the clinicopathological features of oropharyngeal cancer patients in Jordan based on their HPV status. Sixty-nine biopsies from two hospitals were included. Tissue microarrays were prepared from formalin-fixed paraffin-embedded (FFPE) specimens and stained with antibodies for CDKN2A/P16, EGFR, PI3K, PTEN, AKT, pS473AKT, PS2mTOR, and TIMAP. The cohort was divided according to P16 expression. Chi-square test and survival analyses were employed to evaluate the variations among the study variables and determine the prognostic factors, respectively. P16 expression was found in 55.1% of patients; however, there was no significant association between P16 expression and the patients' clinicopathological features. The Kaplan-Meier test revealed that smoking in P16-positive group and younger age (< 58 years) negatively impacted disease-free survival (DFS) (P = 0.04 and P = 0.003, respectively). Multivariate Cox regression test indicated that smoking, age, PI3K, and AKT were negative predictors of DFS (P = 0.021, P = 0.002, P = 0.021, and P = 0.009, respectively), while TIMAP was a positive predictor (P = 0.045). Elevated P16 expression is found in more than half of the patients' specimens. DFS is negatively affected by younger age and the combined effect of smoking and P16 overexpression. TIMAP is overexpressed in P16-positive oropharyngeal cancer, and it is a favorable predictor of DFS.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"136-146"},"PeriodicalIF":1.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140065403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Utility of human epidermal growth factor 2 heterogeneity as a prognostic factor in triple-negative breast cancer","authors":"Eriko Narusawa, Sasagu Kurozumi, Ayaka Katayama, Yukio Koibuchi, Akira Ogawa, Daisuke Takata, Shoko Tokuda, Sayaka Obayashi, Tetsunari Oyama, Jun Horiguchi, Ken Shirabe, Takaaki Fujii","doi":"10.1007/s00795-024-00386-z","DOIUrl":"https://doi.org/10.1007/s00795-024-00386-z","url":null,"abstract":"<p>In some cases of human epidermal growth factor 2 (HER2)-negative breast cancer, including triple-negative breast cancer, HER2 expression is sporadically and strongly upregulated, a condition known as <i>HER2</i> heterogeneity. We investigated the clinicopathological features of patients with <i>HER2</i> heterogeneity in triple-negative breast cancers treated with neoadjuvant chemotherapy. Thirty-nine patients with triple-negative breast cancer who had undergone preoperative chemotherapy participated in this study. To assess for <i>HER2</i> heterogeneity, we used dual in situ hybridization slides. We evaluated the association between <i>HER2</i> heterogeneity and clinicopathological factors such as rates of pathologic complete response (pCR) and of recurrence-free survival. Of the 39 patients, 15 (38.5%) had cancers with <i>HER2</i> heterogeneity. The pCR rates were 13.3% among patients with <i>HER2</i> heterogeneity and 20.8% among those with <i>HER2</i> nonheterogeneity, but the difference was not significant. The recurrence-free survival rate was significantly lower in patients with <i>HER2</i> heterogeneity than in those without (<i>P</i> = 0.025). <i>HER2</i> heterogeneity is a significant predictor of poor prognosis in patients with triple-negative breast cancer treated with neoadjuvant chemotherapy.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":"21 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140573293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Alpha-fetoprotein producing endometrioid carcinoma arising in an adenomyoma of the uterus","authors":"Yuzo Oyama, Takahiro Kusaba, Kasumi Takao, Eri Obata, Mitsutake Yano, Kazuhiro Kawamura, Haruto Nishida, Tsutomu Daa","doi":"10.1007/s00795-024-00384-1","DOIUrl":"https://doi.org/10.1007/s00795-024-00384-1","url":null,"abstract":"<p>We report a case of alpha-fetoprotein-producing endometrioid carcinoma (AFP-EC) that originated within an adenomyoma of the uterine corpus. A 76-year-old Japanese woman was incidentally discovered to have a uterine tumor along with multiple lung nodules. Upon surgical removal of the uterus, it was revealed that the tumor was situated within the adenomyoma. The tumor exhibited microfollicular structures and solid growth patterns, with hyaline globules, clear cell glands, and primitive tumor cells. Immunohistochemical analysis indicated the presence of germ cell markers, including AFP, SALL4, and glypican3, leading to final diagnosis of AFP-EC. Histopathologically, AFP-ECs exhibit characteristics similar to those of AFP-producing neoplasms in other organs. Furthermore, a nomenclature issue arises when distinguishing AFP-ECs from yolk sac tumors of the endometrium in older patients due to their shared features. The concept of retrodifferentiation or neometaplasia suggests that “endometrioid carcinoma with yolk sac tumor differentiation” or “endometrioid carcinoma with a primitive phenotype” may serve as more fitting terms for the diverse spectrum of AFP-producing neoplasms in the endometrium. In conclusion, this case underscores the diagnostic challenges posed by AFP-ECs arising from adenomyomas and emphasizes the need for refining the nomenclature and classification of AFP-producing neoplasms within the endometrium.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":"55 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140097460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Overexpression of SerpinB9 in non-seminomatous germ cell tumors.","authors":"Toshiki Anami, Yuki Ibe, Lianbo Li, Yoshihiro Komohara, Hiroki Hirao, Mamoru Harada, Hiromu Yano, Yukio Fujiwara, Takanobu Motoshima, Junji Yatsuda, Taizo Hibi, Tomomi Kamba","doi":"10.1007/s00795-023-00374-9","DOIUrl":"10.1007/s00795-023-00374-9","url":null,"abstract":"<p><p>Serpinb9 is an inhibitor of granzyme B and is potentially involved in the immune escape of tumor cells. In the present study, bioinformatics analysis using open databases suggested that SerpinB9 is overexpressed in testicular embryonal carcinoma. Immunohistological analysis was performed on 28 cases of testicular germ cell tumors to investigate the relationship between SerpinB9 expression in testicular germ cell tumors and the tumor immune environment. SerpinB9 was significantly upregulated in the non-seminoma group and inversely correlated with the number of tumor-infiltrating CD8-positive cells. In addition, yolk sac tumors were characterized by the loss of human leukocyte antigen-class I expression. These findings suggest that SerpinB9 contributes to the immune escape of testicular germ cell tumors. Targeting therapy for SerpinB9 might therefore be useful in immunotherapy for testicular germ cell tumors resistant to immune checkpoint inhibitors.</p>","PeriodicalId":18338,"journal":{"name":"Medical Molecular Morphology","volume":" ","pages":"68-75"},"PeriodicalIF":1.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138291362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}