Aims: To evaluate the role of the follicular helper T (T(FH)) cell markers, CD10, BCL6, programmed death-1 (PD-1) and CXCL13, in the differential diagnosis of nodal peripheral T cell lymphomas (PTCLs) and to determine whether PTCL subtypes other than angioimmunoblastic T cell lymphoma (AITL) express T(FH) cell markers.
Methods: 162 nodal PTCL specimens and 53 other lymphoid pathology specimens were collected. Immunohistochemistry for CD10, BCL6, PD-1 and CXCL13 was performed on tissue microarray sections. Morphological feature analysis and double labelling assay were also performed.
Results: For AITL cases, the rate of CD10, BCL6, PD-1 and CXCL13 expression was 75.0% (36/48), 66.7% (32/48), 93.8% (45/48) and 97.9% (47/48), respectively. Expression of CD10, PD-1 and CXCL13 in the AITL group was significantly higher than in other nodal PTCLs and the control group (p<0.05). The rate of coexpression of three or four (≥3) markers was 83.3% for AITL cases, which was significantly higher than that for any of the non-AITL cases (0-4.9%; p<0.05). The rate of coexpression of PD-1 and CXCL13 (91.7%, 44/48) was significantly higher than that of CD10 and BCL6 (56.3%, 27/48) (p=0.000) in the AITL group. Seventeen cases of PTCL not otherwise specified (PTCL, NOS) expressed CXCL13, including both cases of the follicular variant of PTCL, NOS (FVPTCL, NOS), three of the four cases of the lymphoepithelioid variant of PTCL, NOS (LVPTCL, NOS), and the remaining 12 cases which displayed one or more features of AITL.
Conclusions: The combined detection of CD10, BCL6, PD-1 and CXCL13 has high specificity and sensitivity for the differential diagnosis of AITL. PD-1 and CXCL13 are more sensitive, superior diagnostic markers for AITL than CD10 and BCL6. Currently, T(FH) cell markers are the only available markers that show high specificity for AITL. LVPTCL, NOS and/or FVPTCL, NOS may also arise from T(FH) cells and fall within the spectrum of AITL.
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http://dx.doi.org/10.1136/jcp.2010.084459 | DOI Listing |
Front Immunol
December 2024
Department of Medicine, Harvard Medical School, Boston, MA, United States.
The potent immunostimulatory effects of toll-like receptor 8 (TLR8) agonism in combination with PD-1 blockade have resulted in various preclinical investigations, yet the mechanism of action in humans remains unknown. To decipher the combinatory mode of action of TLR8 agonism and PD-1 blockade, we employed a unique, open-label, phase 1b pre-operative window of opportunity clinical trial (NCT03906526) in head and neck squamous cell carcinoma (HNSCC) patients. Matched pre- and post-treatment tumor biopsies from the same lesion were obtained.
View Article and Find Full Text PDFJ Immunother Cancer
November 2024
Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, Shanghai, China
J Transl Autoimmun
December 2024
Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Objective: Dysregulated T cell homeostasis has long been implicated in the pathogenesis of rheumatoid arthritis (RA), in the joint of which peripheral helper T (Tph) cells accumulate and form ectopic lymphoid organs. We examined whether homeostatic signals are involved in the development of Tph cells.
Methods: Human peripheral blood mononuclear cells were cultured with IL-7, the critical cytokine for T cell homeostasis.
The intratumoral microbiome has recently emerged as a new hallmark of cancer, with implications for response or resistance to therapy. While bacteria can either promote or inhibit cancer growth, intratumoral bacteria can also be engineered using synthetic biology to remodel the tumor microenvironment. Here, we engineered the probiotic bacterium Nissle 1917 (EcN) to express the human chemokine CXCL13, a critical component of germinal center (GC) formation.
View Article and Find Full Text PDFGastroenterology
October 2023
Department of Immunology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Gusu School, Nanjing Medical University, Nanjing 211166, Jiangsu, China; Department of Central Laboratory, The Affiliated Huai'an No.1 People's Hospital, Nanjing Medical University, Huai'an 223300, P. R. China; Department of General Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University Nanjing 210009, China. Electronic address:
Background & Aims: Although the presence of tertiary lymphoid structures (TLS) correlates with positive responses to immunotherapy in many solid malignancies, the mechanism by which TLS enhances anti-tumor immunity is not well understood. The present study aimed to investigate the underlying cross-talk circuits between B cells and tissue-resident memory T (Trm) cells within the TLS and to understand their role in the context of immunotherapy.
Methods: Immunostaining and hematoxylin and eosin staining of TLS and CXCL13CD103CD8Trm cells were performed on tumor sections from patients with gastric cancer (GC).
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