CCL22 mutations drive natural killer cell lymphoproliferative disease by deregulating microenvironmental crosstalk

Baer, Constance; Kimura, Shunsuke; Rana, Mitra S.; Kleist, Andrew B.; Flerlage, Tim; Feith, David J.; Chockley, Peter; Walter, Wencke; Meggendorfer, Manja; Olson, Thomas L.; Cheon, HeeJin; Olson, Kristine C.; Mueller, Martha-Lena; Foran, James M.; Janke, Laura J.; Qu, Chunxu; Porter, Shaina N.; Pruett-Miller, Shondra M.; Kalathur, Ravi C.; Haferlach, Claudia; Kern, Wolfgang; Paietta, Elisabeth; Thomas, Paul G.; Babu, M. Madan; Loughran, Thomas P.; Iacobucci, Ilaria; Haferlach, Torsten; Mullighan, Charles G.

doi:10.1038/s41588-022-01059-2

Cited by 28 publications

(20 citation statements)

References 88 publications

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“…352,354,355 Other genes have been found recurrently (TNFAIP3) and occasionally (eg, BCL11B, FLT3, PTPN23) mutated in patients with T-LGLL. 353 Mutations of STAT3 (~30%) 356 , TET2 (~25%), and CCL22 (27%) 357 have been detected in NK-LGLL, while this disorder appears to be devoid of STAT5B genetic lesions. [358][359][360] TNFAIP3 mutation has been found in ~6% of NK-LGLL.…”

Section: Extranodal Ptclsmentioning

confidence: 99%

Genomic profiling for clinical decision making in lymphoid neoplasms

Leval

Alizadeh

Bergsagel

et al. 2022

Blood

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With the introduction of large-scale molecular profiling methods and high-throughput sequencing technologies, the genomic features of most lymphoid neoplasms have been characterized at an unprecedented scale. While the principles for the classification and diagnosis of these disorders, founded on a multidimensional definition of disease entities, have been consolidated over the past 25 years, novel genomic data have markedly enhanced our understanding of lymphomagenesis and enriched the description of disease entities at the molecular level. Yet the current diagnosis of lymphoid tumors is largely based on morphological assessment and immunophenotyping, with only few entities being defined by genomic criteria. This paper, which accompanies the International Consensus Classification of mature lymphoid neoplasms, will address how established assays and newly developed technologies for molecular testing already complement clinical diagnoses and provide a novel lens on disease classification. More specifically, their contributions to diagnosis refinement, risk stratification and therapy prediction will be considered for the main categories of lymphoid neoplasms. The potential of whole-genome sequencing, circulating tumor DNA analyses, single-cell analyses and epigenetic profiling will be discussed, as these will likely become important future tools for implementing precision medicine approaches in clinical decision-making for patients with lymphoid malignancies.

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Section: Extranodal Ptclsmentioning

confidence: 99%

Genomic profiling for clinical decision making in lymphoid neoplasms

Leval

Alizadeh

Bergsagel

et al. 2022

Blood

View full text Add to dashboard Cite

show abstract

“…It’s known that different immune cell subsets can be recruited into TME via interactions between chemokines and chemokine receptors, and affect tumor progression and therapeutic outcome [ 66 ]. Chemokines (CXCL12 [ 67 ], CXCL8 [ 68 ], CXCL5 [ 69 ]) and chemokine receptors (CXCR1/2 [ 70 ], CCR4 [ 71 , 72 ], CCR8 [ 73 ]) are well-known to deeply participate in the tumor development and progression in various cancers, including LUAD [ 74 ]. In the present study, we found that the expression of KIAA1199 was correlated with the levels of many chemokines (CXCL12, CXCL8, CXCL5) and chemokine receptors (CXCR1/2, CXCR4, CCR8) in LUAD.…”

Section: Discussionmentioning

confidence: 99%

KIAA1199 Correlates With Tumor Microenvironment and Immune Infiltration in Lung Adenocarcinoma as a Potential Prognostic Biomarker

Shen¹,

Mo²,

Tan³

et al. 2022

Pathol. Oncol. Res.

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Background: KIAA1199 has been considered a key regulator of carcinogenesis. However, the relationship between KIAA1199 and immune infiltrates, as well as its prognostic value in lung adenocarcinoma (LUAD) remains unclear.Methods: The expression of KIAA1199 and its influence on tumor prognosis were analyzed using a series of databases, comprising TIMER, GEPIA, UALCAN, LCE, Prognoscan and Kaplan-Meier Plotter. Further, immunohistochemistry (IHC), western blot (WB) and receiver operating characteristic (ROC) curve analyses were performed to verify our findings. The cBioPortal was used to investigate the genomic alterations of KIAA1199. Prediction of candidate microRNA (miRNAs) and transcription factor (TF) targeting KIAA1199, as well as GO and KEGG analyses, were performed based on LinkedOmics. TIMER and TISIDB databases were used to explore the relationship between KIAA1199 and tumor immune infiltration.Results: High expression of KIAA1199 was identified in LUAD and Lung squamous cell carcinoma (LUSC) patients. High expression of KIAA1199 indicated a worse prognosis in LUAD patients. The results of IHC and WB analyses showed that the expression level of KIAA1199 in tumor tissues was higher than that in adjacent tissues. GO and KEGG analyses indicated KIAA1199 was mainly involved in extracellular matrix (ECM)-receptor interaction and extracellular matrix structure constituent. KIAA1199 was positively correlated with infiltrating levels of CD4+ T cells, macrophages, neutrophil cells, dendritic cells, and showed positive relationship with immune marker subsets expression of a variety of immunosuppressive cells.Conclusion: High expression of KIAA1199 predicts a poor prognosis of LUAD patients. KIAA1199 might exert its carcinogenic role in the tumor microenvironment via participating in the extracellular matrix formation and regulating the infiltration of immune cells in LUAD. The results indicate that KIAA1199 might be a novel biomarker for evaluating prognosis and immune cell infiltration in LUAD.

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“…CD194 (CCR4) is the receptor for two chemokines, CCL17 and CCL22, expressed on Type 2 helper T-cells (Th2) and Treg. Its expression is high in mature T-cells, and it has been shown to be implicated in the homing of leukocytes to inflamed sites [ 182 ]. Mogamulizumab is an anti-CCR4 humanized antibody, which has been approved in Japan since 2014 for patients with adult T-cell leukemia.…”

Section: T-cell Surface Antigens As Immunotherapeutic Target For T-allmentioning

confidence: 99%

The emerging scenario of immunotherapy for T-cell Acute Lymphoblastic Leukemia: advances, challenges and future perspectives

et al. 2023

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T-cell acute lymphoblastic leukemia (T-ALL) is a challenging pediatric and adult haematologic disease still associated with an unsatisfactory cure rate. Unlike B-ALL, the availability of novel therapeutic options to definitively improve the life expectancy for relapsed/resistant patients is poor. Indeed, the shared expression of surface targets among normal and neoplastic T-cells still limits the efficacy and may induce fratricide effects, hampering the use of innovative immunotherapeutic strategies. However, novel monoclonal antibodies, bispecific T-cell engagers (BTCEs), and chimeric antigen receptors (CAR) T-cells recently showed encouraging results and some of them are in an advanced stage of pre-clinical development or are currently under investigation in clinical trials. Here, we review this exciting scenario focusing on most relevant advances, challenges, and perspectives of the emerging landscape of immunotherapy of T-cell malignancies.

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CCL22 mutations drive natural killer cell lymphoproliferative disease by deregulating microenvironmental crosstalk

Cited by 28 publications

References 88 publications

Genomic profiling for clinical decision making in lymphoid neoplasms

Genomic profiling for clinical decision making in lymphoid neoplasms

KIAA1199 Correlates With Tumor Microenvironment and Immune Infiltration in Lung Adenocarcinoma as a Potential Prognostic Biomarker

The emerging scenario of immunotherapy for T-cell Acute Lymphoblastic Leukemia: advances, challenges and future perspectives

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