TNFRSF9

Case study 1: Kang Yi Lee, 2021

Rhabdomyosarcoma (RMS) is a heterogeneous soft tissue neoplasm most frequently found in children and adolescents. As the prognosis for recurrent and metastatic RMS remains poor, immunotherapies are hoped to improve quality of life and survival. But it was puzzling to find expression of CD137 on an RMS tissue microarray by multiplex staining. Functional in vitro experiments demonstrate that CD137 on RMS cells is being transferred to adjacent antigen-presenting cells by trogocytosis, where it downregulates CD137 ligand, and thereby reduces T cell costimulation which results in reduced killing of RMS cells. The transfer of CD137 and the subsequent downregulation of CD137 ligand is a physiological negative feedback mechanism that is likely usurped by RMS, and may facilitate its escape from immune surveillance. This study implicates ectopic CD137 expression as a pathogenesis mechanism in RMS, and it demonstrates that CD137 may be a novel target for immunotherapy of RMS.

Fig1. Rd18, Rh41, Rd and JR1 cells were cultured with 75 ng/ml of TNF for 24 h. CD137 expression was measured by flow cytometry.

Fig2. Anti-CD137 CAR-KHYG-1 cells specifically kill CD137-expressing RMS cells. Percentages of RMS cell TNF level. Top row: Rd18 cells, bottom row: Rh41 cells.

Case study 2: Benjamin I Philipson, 2020

Clinical response to chimeric antigen receptor (CAR) T cell therapy is correlated with CAR T cell persistence, especially for CAR T cells that target CD19+ hematologic malignancies. 4-1BB-costimulated CAR (BBζ) T cells exhibit longer persistence after adoptive transfer than do CD28-costimulated CAR (28ζ) T cells. 4-1BB signaling improves T cell persistence even in the context of 28ζ CAR activation, which indicates distinct prosurvival signals mediated by the 4-1BB cytoplasmic domain. To specifically study signal transduction by CARs, we developed a cell-free, ligand-based activation and ex vivo culture system for CD19-specific CAR T cells.

This study showed that only BBζ CARs activated noncanonical nuclear factor κB (ncNF-κB) signaling in T cells basally and that the anti-CD19 BBζ CAR further enhanced ncNF-κB signaling after ligand engagement. Although the findings do not exclude the importance of other signaling differences between BBζ and 28ζ CARs, they demonstrate the necessary and nonredundant role of ncNF-κB signaling in promoting the survival of BBζ CAR T cells.

Fig3. Representative ex vivo expansion of the indicated CAR T cells stimulated by irradiated Nalm6 target cells at the indicated times at a T cell to target cell ratio of 2:1.

Fig4. Representative Western blotting analysis of the cytoplasmic and nuclear fractions from anti-CD19 BBζ CAR T cells before and at the indicated times after the addition of target beads.

TNFRSF9 involved in several pathways and played different roles in them. We selected most pathways TNFRSF9 participated on our site, such as Cytokine-cytokine receptor interaction, which may be useful for your reference. Also, other proteins which involved in the same pathway with TNFRSF9 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

TNFRSF9 has several biochemical functions, for example, receptor activity, tumor necrosis factor-activated receptor activity. Some of the functions are cooperated with other proteins, some of the functions could acted by TNFRSF9 itself. We selected most functions TNFRSF9 had, and list some proteins which have the same functions with TNFRSF9. You can find most of the proteins on our site.

TNFRSF9 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with TNFRSF9 here. Most of them are supplied by our site. Hope this information will be useful for your research of TNFRSF9.

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