MALIGNANT T CELL ACTIVATION BY A BACILLUS SPECIES ISOLATED FROM CUTANEOUS T CELL LYMPHOMA LESIONS

Due to the high expression of P-selectin glycoprotein ligand-1 (PSGL-1) in lymphoproliferative disorders and in multiple myeloma, it has been considered as a potential target for humoral immunotherapy, as well as an immune checkpoint inhibitor in T-cells. By investigating the expression of SELPLG in 678 T- and B-cell samples by gene expression profiling (GEP), further supported by tissue microarray and immunohistochemical analysis, we identified anaplastic large T-cell lymphoma (ALCL) as constitutively expressing SELPLG at high levels. Moreover, GEP analysis in CD30+ ALCLs highlighted a positive correlation of SELPLG with TNFRSF8 (CD30-coding gene) and T-cell receptor (TCR)-signaling genes (LCK, LAT, SYK and JUN), suggesting that the common dysregulation of TCR expression in ALCLs may be bypassed by the involvement of PSGL-1 in T-cell activation and survival. Finally, we evaluated the effects elicited by in vitro treatment with two anti-PSGL-1 antibodies (KPL-1 and TB5) on the activation of the complement system and induction of apoptosis in human ALCL cell lines. In conclusion, our data demonstrated that PSGL-1 is specifically enriched in ALCLs, altering cell motility and viability due to its involvement in CD30 and TCR signaling, and it might be considered as a promising candidate for novel immunotherapeutic approaches in ALCLs.

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Enhanced Expression of T-Cell Activation and Natural Killer Cell Antigens Indicates Systemic Anti-Tumor Response in Early Primary Cutaneous T-Cell Lymphoma

Journal of Investigative Dermatology ◽

10.1111/1523-1747.ep12292129 ◽

1997 ◽

Vol 108 (5) ◽

pp. 743-747 ◽

Cited By ~ 40

Author(s):

Khusru Asadullah ◽

Markus Friedrich ◽

Wolf-Dietrich Döcke ◽

Sigbert Jahn ◽

Hans-Dieter Volk ◽

...

Keyword(s):

T Cell ◽

Natural Killer Cell ◽

T Cell Activation ◽

Cell Activation ◽

Tumor Response ◽

Cell Lymphoma ◽

Killer Cell ◽

Cutaneous T Cell Lymphoma ◽

Enhanced Expression ◽

Early Primary

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Correlation of mutational landscape and survival outcome of peripheral T-cell lymphomas

Experimental Hematology and Oncology ◽

10.1186/s40164-021-00200-x ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Yingying Ye ◽

Ning Ding ◽

Lan Mi ◽

Yunfei Shi ◽

Weiping Liu ◽

...

Keyword(s):

T Cell ◽

Clinical Outcomes ◽

T Cell Activation ◽

Cell Activation ◽

Cell Lymphoma ◽

Negative Impact ◽

Chromatin Modification ◽

Progression Free Survival ◽

Survival Outcome ◽

T Cell Lymphoma

Abstract Objective To explore the correlation of mutation landscape with clinical outcomes in patients with peripheral T-cell lymphoma (PTCL). Methods We retrospectively analyzed the clinicopathological and prognosis data of 53 patients with PTCL from November 2011 to December 2017. Targeted next-generation sequencing of a 659-gene panel was performed for tissues from 53 patients with PTCLs. The correlation of mutation landscape with clinical outcomes was analyzed. Results TET2 was the most frequently mutated gene (64%), followed by RHOA (43%), PCLO (23%), DNMT3A (19%), IDH2 (17%), PIEZO1 (17%) and TP53 (15%). When mutated genes were categorized into functional groups, the most common mutations were those involved in epigenetic/chromatin modification (75%), T-cell activation (74%), and the DNA repair/TP53 pathway (64%). TET2/TP53 mutations were significantly associated with positive B symptoms (P = 0.045), and elevated lactate dehydrogenase (LDH) level (P = 0.011). Moreover, TET2/TP53 mutation was a risk factor for PTCL patient survival (HR 3.574, 95% CI 1.069 − 11.941, P = 0.039). The occurrence of JAK/STAT pathway mutations in angioimmunoblastic T-cell lymphoma (AITL) patients conferred a worse progression-free survival (HR 2.366, 95% CI 0.9130–6.129, P = 0.0334). Conclusions Heterogeneous gene mutations occur in PTCL, some of which have a negative impact on the survival outcome.

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