# Memory T‐Cell Phenotype in Cutaneous T‐Cell Lymphoma Is Modified by Germline Gene Gametocyte Specific Factor 1

## TL;DR

This study shows that the protein GTSF1 modifies memory T-cell traits in skin T-cell lymphoma, potentially worsening prognosis and offering a new treatment target.

## Contribution

The study reveals a novel role of GTSF1 in modifying T-cell phenotypes and immune responses in CTCL, linking it to disease progression and prognosis.

## Key findings

- GTSF1 knockdown in CTCL cells increases T-cell activation and cytokine production.
- High GTSF1 expression correlates with worse prognosis in CTCL patients.
- GTSF1 helps malignant T cells adopt a memory phenotype with reduced immune responsiveness.

## Abstract

Cutaneous T‐cell lymphoma (CTCL) is a heterogeneous group of lymphoproliferative disorders characterised by skin infiltration by malignant memory T cells. While most patients will present with an indolent disease, others will follow a highly aggressive clinical course. Currently, defining disease prognosis remains challenging. Ectopic expression of gametocyte‐specific factor 1 (GTSF1) has emerged as a potential prognostic biomarker. However, its contribution to CTCL carcinogenesis remains unknown. Here, we report that GTSF1 contributes to carcinogenesis by partially modifying the memory/effector phenotype of the malignant T cells. GTSF1 knockdown in CTCL cells led to T‐cell activation and production of IFNγ and TNFα. Advanced stages of the disease are associated with decreased production of these cytokines. Notably, we show that patients classified with high expression of GTSF1 are associated with a worse disease prognosis. Taken together, our findings indicate that GTSF1 expression in CTCL cells allows them to acquire memory T‐cell phenotype. Malignant memory T cells have a decreased production of immune‐responsive cytokines, leading to a diminished immune response and disease progression. GTSF1 is an important candidate as a prognostic biomarker. Furthermore, understanding the specific function of GTSF1 might help develop novel targeted treatment options for CTCL patients.