ABSTRACT
Tumor-associated myeloid-derived cells (MDCs) significantly impact cancer prognosis and treatment responses due to their remarkable plasticity and tumorigenic behaviors. Here, we integrate single-cell RNA-sequencing data from different cancer types, identifying 29 MDC subpopulations within the tumor microenvironment. Our analysis reveals abnormally expanded MDC subpopulations across various tumors and distinguishes cell states that have often been grouped together, such as TREM2+ and FOLR2+ subpopulations. Using deconvolution approaches, we identify five subpopulations as independent prognostic markers, including states co-expressing TREM2 and PD-1, and FOLR2 and PDL-2. Additionally, TREM2 alone does not reliably predict cancer prognosis, as other TREM2+ macrophages show varied associations with prognosis depending on local cues. Validation in independent cohorts confirms that FOLR2-expressing macrophages correlate with poor clinical outcomes in ovarian and triple-negative breast cancers. This comprehensive MDC atlas offers valuable insights and a foundation for futher analyses, advancing strategies for treating solid cancers.
Subject(s)
Membrane Glycoproteins , Myeloid Cells , Neoplasms , Receptors, Immunologic , Single-Cell Analysis , Tumor Microenvironment , Humans , Single-Cell Analysis/methods , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology , Myeloid Cells/metabolism , Myeloid Cells/pathology , Receptors, Immunologic/metabolism , Receptors, Immunologic/genetics , Membrane Glycoproteins/metabolism , Membrane Glycoproteins/genetics , Prognosis , Neoplasms/genetics , Neoplasms/pathology , Neoplasms/metabolism , Female , Programmed Cell Death 1 Receptor/metabolism , Programmed Cell Death 1 Receptor/genetics , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/metabolism , Ovarian Neoplasms/pathology , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , B7-H1 Antigen/metabolism , B7-H1 Antigen/geneticsABSTRACT
The histologic features of cervical intraepithelial neoplasia (CIN 1), caused by infection by the human papillomavirus (HPV), can overlap with those of its mimics that can lead to an over diagnosis of this sexually transmitted disease. In this study, 67 consecutive cervical biopsies that were diagnosed as CIN 1 from the surgical files of Ohio State University Medical Center were analyzed. Twenty controls (10 CIN 1 cervical biopsies and 10 normal cervical tissues) were also studied. The 87 biopsies were reevaluated blinded to the original diagnosis and the results were correlated with detection of HPV DNA by in situ hybridization and glycogen by the periodic acid solution (PAS)/PAS-D stain, respectively. HPV was detected by in situ hybridization in 55/67 cases (82%); no virus was evident in the negative controls whereas each of the 10 CIN 1 controls was virus positive. A PAS test demonstrated in the mature squamous component of the negative controls a strong signal in cells with prominent and uniform halos, which was lost with diastase treatment, indicative of abundant glycogen. The PAS/PAS-D tests in the CIN 1 lesions showed rare variable sized glycogen deposits in the dysplastic cells. Nine (15%) cases initially diagnosed as CIN 1 were HPV negative by in situ hybridization and had halolike cells that were strongly and uniformly positive for glycogen. This data underscores the value of glycogen and HPV analyses in improving the specificity of the diagnosis of CIN 1.
Subject(s)
Papillomavirus Infections/diagnosis , Periodic Acid-Schiff Reaction , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Neoplasms/diagnosis , Female , Humans , In Situ Hybridization , Papillomaviridae , Papillomavirus Infections/complications , Sensitivity and Specificity , Uterine Cervical Neoplasms/virology , Uterine Cervical Dysplasia/virologyABSTRACT
The mechanism by which the virus associated with dengue fever can cause a fatal hepatitis is not well understood. The purpose of this study was to examine 9 cases of fatal dengue hemorrhagic fever-associated hepatitis, and to correlate the histologic findings with viral detection and cytokine response. The histologic changes were nonspecific and included massive hepatic necrosis and a pauci-cellular acute hepatitis. Viral cDNA detection by reverse transcriptase in situ polymerase chain reaction demonstrated that the fatal hepatitis was due to infection on average of >90% of hepatocytes and many Kupffer cells. Similar results were obtained using immunohistochemistry for viral protein using an automated highly sensitive system. Immunohistochemical analysis for tumor necrosis factor alpha, and interleukin-2, showed rare positive Kupffer cells. In comparison, fatal cases of hepatitis C associated liver failure demonstrated far fewer infected hepatocytes and a concomitant strong up-regulation of many cytokines, notably tumor necrosis factor alpha and interleukin-2. It is concluded that fatal dengue hemorrhagic fever is associated with acute, severe liver damage due primarily to massive direct infection of hepatocytes and Kupffer cells with minimal cytokine response. The infection can be readily detected in a few hours using an automated system that has a sensitivity equivalent to reverse transcriptase in situ polymerase chain reaction.