Ret mouse very large tumors (VLTs) display altered ratios of infiltrating memory to naive T cells

• Verfasst von: Khan, Mohammad Wasim Kayyum [VerfasserIn]
• Verfasst von: Umansky, Viktor [VerfasserIn]
• Titel: Ret mouse very large tumors (VLTs) display altered ratios of infiltrating memory to naive T cells
• Titelzusatz: roles in tumor expansion
• Verf.angabe: Mohammad W. Khan, Viktor Umansky
• E-Jahr: 2016
• Jahr: September 2016
• Umfang: 10 S.
• Fussnoten: Gesehen am 11.12.2019 ; Available online 27 June 2016
• Titel Quelle: Enthalten in: Pathophysiology
• Ort Quelle: Amsterdam [u.a.] : Elsevier, 1994
• Jahr Quelle: 2016
• Band/Heft Quelle: 23(2016), 3, Seite 211-220
• ISSN Quelle: 1873-149X
• DOI: doi:10.1016/j.pathophys.2016.06.001
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Central memory
• Sach-SW: Effector memory
• Sach-SW: Melanoma
• Sach-SW: Ret mice
• Sach-SW: TILs
• Sach-SW: Tregs
• Sach-SW: Very large tumors
• K10plus-PPN: 168517843X

Abstract

Melanoma is an aggressive skin cancer, however it is immunogenic. The size of the primary tumor is associated with the nodal metastases. Our goals were to characterize melanoma-associated antigens (MAAs) and tumor-infiltrating T-lymphocytes (TILs) subsets in the few very large tumors (VLTs) developing in ret transgenic mice of melanoma. Tumors >700mg (VLTs) were investigated for MAAs and subsets of TILs. Immunohistochemistry and flow cytometry-based studies were performed to determine the infiltration patterns of T-lymphocytes in VLTs. It was observed that zinc fixative restores the antigenicity of the cell-surface markers of lymphocyte subpopulations without the need of antigen retrieval, whereas formalin-based fixative fails to restore the antigenicity in the presence of antigen retrieval in the immunohistochemistry. VLTs from ret mice express MAAs, such as Tyrosinase, TRP-1, TRP-2 and gp-100. The mean±standard deviation (S.D.) T-cell infiltration per 400 times-high power field in VLTs; CD4+ (2.33±1.3), CD8+ (2.00±1.0), and CD4+ Foxp3+ (2.5±0.5) regulatory T cells infiltration was exclusively restricted to the tumor stroma. Moreover, our flow cytometry-based data reveal that % mean±S.D. naive CD3+ CD4+ T cell infiltration (32.8±4.0%) was significantly larger than effector (25.8±2.8%, p<0.01) and central memory cells (16.1±3.7%, p<0.001) in VLTs. Similarly, between CD3+ CD8+ T cells, naive cells infiltrate (57.7±2.3%) in a significantly larger frequency than effector (5.0±0.4%, p<0.0001) and central memory cell (4.8±1.7%, p<0.0001) subsets. These results suggest that the VLTs from ret mice display lowered infiltration ratios between memory and naive T cells, which could be associated with the relatively large growth of VLTs.