Genetic Subtypes of Systemic Anaplastic Large Cell Lymphoma Show Distinct Differences in PD-L1 Expression and Regulatory and Cytotoxic T Cells in the Tumor Microenvironment.


Journal

Applied immunohistochemistry & molecular morphology : AIMM
ISSN: 1533-4058
Titre abrégé: Appl Immunohistochem Mol Morphol
Pays: United States
ID NLM: 100888796

Informations de publication

Date de publication:
01 2020
Historique:
entrez: 7 12 2019
pubmed: 7 12 2019
medline: 24 11 2020
Statut: ppublish

Résumé

Anaplastic large cell lymphomas (ALCL) encompass several subgroups that differ in their clinical presentation, genetic features, and prognosis. We characterized the genetic subgroups of 74 patients with ALCL and correlated programmed death ligand 1 (PD-L1) protein expression and compared the densities and ratios of FOXP3+ T regulatory cells and CD8+ tumor-infiltrating lymphocytes (TILs) in tumor cells and the immune microenvironment. The subgroups included anaplastic lymphoma kinase (ALK)-positive (ALK+) ALCL and ALK-negative (ALK-) ALCL and DUSP22-rearranged and nonrearranged ALK- ALCL. None of our cases represented the TP63-rearrangement ALK- ALCL subgroup. Our results showed that ALK+ ALCL had a higher expression of PD-L1 in the tumor cells, in contrast to ALK- ALCL, which expressed high PD-L1 in tumor-associated macrophages (TAMs). DUSP22-rearranged ALK- ALCL lacked PD-L1 expression in the tumor cells and instead expressed PD-L1 only in TAMs. There was a significant positive correlation of PD-L1 expression between tumor and TAMs in ALK+ ALCL with a negative correlation in ALK- ALCL. Systemic ALCL subgroups had similar densities of CD8+ tumor-infiltrating lymphocytes and FOXP3 T regulatory cells, but differences were observed in the ratio of CD8/FOXP3. Our results suggest that alterations in tumor microenvironment and immune responses exist among systemic ALCL subgroups and these features may account for different clinical behavior and prognosis.

Identifiants

pubmed: 31809310
doi: 10.1097/PAI.0000000000000798
pii: 00129039-202001000-00002
doi:

Substances chimiques

B7-H1 Antigen 0
CD274 protein, human 0
TP63 protein, human 0
Transcription Factors 0
Tumor Suppressor Proteins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

10-16

Références

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Auteurs

Cristiane R Ferreira (CR)

Department of Pathology, Stanford University School of Medicine, Stanford, CA.
Departments of Pathology.

Vidhya Manohar (V)

Department of Pathology, Stanford University School of Medicine, Stanford, CA.

Shuchun Zhao (S)

Department of Pathology, Stanford University School of Medicine, Stanford, CA.

Charles D Bangs (CD)

Department of Pathology, Stanford University School of Medicine, Stanford, CA.

Athena Cherry (A)

Department of Pathology, Stanford University School of Medicine, Stanford, CA.

Raymundo Soares Azevedo (RS)

Hematology, University of Sao Paulo, Sao Paulo, Brazil.

Luis A P C Lage (LAPC)

Hematology, University of Sao Paulo, Sao Paulo, Brazil.

Juliana Pereira (J)

Hematology, University of Sao Paulo, Sao Paulo, Brazil.

Maria C N Zerbini (MCN)

Departments of Pathology.

Dita Gratzinger (D)

Department of Pathology, Stanford University School of Medicine, Stanford, CA.

Yasodha Natkunam (Y)

Department of Pathology, Stanford University School of Medicine, Stanford, CA.

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