Distinctive CD8+ T cell and MHC class I signatures in polycythemia vera patients

Cardoso, Elsa M.; Esgalhado, André J.; Patrão, Luís; Santos, Mónica; Neves, Vasco Pinto; Martinez, Jorge; Patto, Maria Da Assunção Vaz; Silva, Helena; Arosa, Fernando A.

doi:10.1007/s00277-018-3332-7

Cited by 10 publications

(8 citation statements)

References 58 publications

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“…In addition, patients with PV have increased levels of terminally differentiated CD8+ T cells and lower levels of naïve T-cells compared to healthy age-matched controls. They also display lower levels of stable cell surface human leukocyte antigen (HLA)-I [64].…”

Section: Immune-subversive Mechanisms In Mpnmentioning

confidence: 99%

Cancer Immune Therapy for Philadelphia Chromosome-Negative Chronic Myeloproliferative Neoplasms

Holmström

Hasselbalch

Andersen

2020

Cancers

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Philadelphia chromosome-negative chronic myeloproliferative neoplasms (MPN) are neoplastic diseases of the hematopoietic stem cells in the bone marrow. MPN are characterized by chronic inflammation and immune dysregulation. Of interest, the potent immunostimulatory cytokine interferon-α has been used to treat MPN for decades. A deeper understanding of the anti-cancer immune response and of the different immune regulatory mechanisms in patients with MPN has paved the way for an increased perception of the potential of cancer immunotherapy in MPN. Therapeutic vaccination targeting the driver mutations in MPN is one recently described potential new treatment modality. Furthermore, T cells can directly react against regulatory immune cells because they recognize proteins like arginase and programmed death ligand 1 (PD-L1). Therapeutic vaccination with arginase or PD-L1 therefore offers a novel way to directly affect immune inhibitory pathways, potentially altering tolerance to tumor antigens like mutant CALR and mutant JAK2. Other therapeutic options that could be used in concert with therapeutic cancer vaccines are immune checkpoint–blocking antibodies and interferon-α. For more advanced MPN, adoptive cellular therapy is a potential option that needs more preclinical investigation. In this review, we summarize current knowledge about the immune system in MPN and discuss the many opportunities for anti-cancer immunotherapy in patients with MPN.

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Section: Immune-subversive Mechanisms In Mpnmentioning

confidence: 99%

Cancer Immune Therapy for Philadelphia Chromosome-Negative Chronic Myeloproliferative Neoplasms

Holmström

Hasselbalch

Andersen

2020

Cancers

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“…Recent data provide evidence for coreactive CD8+ T-cells in hematologic diseases such as polycythemia vera [16], but with an immunophenotype different from the aberrant T-cell population described here.…”

Section: Discussionmentioning

confidence: 52%

Aberrant CD3-Positive, CD8-Low, CD7-Negative Lymphocytes May Appear During Viral Infections and Mimic Peripheral T-Cell Lymphoma

et al. 2020

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Flow cytometry (FC) facilitates diagnosis of peripheral T-cell non-Hodgkin lymphoma (T-NHL), but overlapping features between reactive and neoplastic T-cell proliferations often hamper a rapid assessment. One hundred forty peripheral blood samples submitted to diagnostic FC for T-cell immunophenotyping were retrospectively analyzed. A T-cell population with a conspicuous aberrant surface epitope expression pattern was observed in 18 cases and diagnostic follow up was performed. The aberrant T-cell population exhibited a low scatter profile, a CD7-negative/low, CD8-low and CD3-positive immunophenotype, and monoclonal T-cell receptor expansion. T-NHL was ruled out by follow up in all cases. Epstein-Barr virus infection was diagnosed in 12 cases, cytomegalovirus infection in three cases; one patient had been vaccinated. The irregular subpopulation disappeared spontaneously within days or weeks. We describe a novel peripheral blood T-cell subpopulation with a low light scatter and CD8-low, CD7-negative/low and CD3-positive marker expression profile, which indicates reactive T-cell expansion in patients who present with peripheral lymphadenopathy and/or B symptoms.

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“…In the current study, we found that T-cell subsets of patients with MF shifted from a quiescent to an activated state and that treatment with ruxolitinib reduced the activation of both helper CD4 and cytotoxic CD8 T cells in a time-dependent manner (Figure 8). The activation pattern of CD8 + T cells was significantly similar to that of polycythemia vera, 31 including decreased TN and TCM, unaltered TEM and increased TEFF subsets. However, in MF, CD4 + cells were also considerably skewed toward an effector cell phenotype, unlike polycythemia vera.…”

Section: Discussionmentioning

confidence: 60%

Altered T-cell subset repertoire affects treatment outcome of patients with myelofibrosis

et al. 2020

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Phenotypic characterization of T cells in myelofibrosis (MF) is intriguing owing to increased inflammation, markedly elevated pro-inflammatory cytokines, and altered distribution of T-cell subsets. Constitutive activation of Janus kinase-2 (JAK2) in the majority of MF patients contributes to the expression of the programmed cell death protein-1 (PD1) and T-cell exhaustion. We wondered whether T-cell activation affects treatment outcome of patients with MF and sought to determine whether the JAK1/2 inhibitor ruxolitinib affects the activation of T-cell subsets. T cells from 47 MF patients were analyzed and the percent of either helper (CD4+) or cytotoxic (CD8+) naive, central memory, effector memory, or effector T cells; and fractions of PD1-expressing cells in each subset were assessed. An increased number of T cells coexpressing CD4/PD1 and CD8/PD1 in MF compared to healthy controls (n=28) was found, and the T cells were significantly skewed toward an effector phenotype in both CD4+ and CD8+ subsets, consistent with a shift from a quiescent to an activated state. Over the course of ruxolitinib treatment, the distribution of aberrant T-cell subsets significantly reversed towards resting cell phenotypes. CD4+ and CD8+ subsets at baseline correlated with monocyte and platelet counts, and their PD1-positive fractions correlated with leukocyte counts and spleen size. Low numbers of PD1+/CD4+ and PD1+/CD8+ cells were associated with complete resolution of palpable splenomegaly and improved survival rate, suggesting that low levels of exhausted T cells confer a favorable response to ruxolitinib treatment.

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Distinctive CD8+ T cell and MHC class I signatures in polycythemia vera patients

Cited by 10 publications

References 58 publications

Cancer Immune Therapy for Philadelphia Chromosome-Negative Chronic Myeloproliferative Neoplasms

Cancer Immune Therapy for Philadelphia Chromosome-Negative Chronic Myeloproliferative Neoplasms

Aberrant CD3-Positive, CD8-Low, CD7-Negative Lymphocytes May Appear During Viral Infections and Mimic Peripheral T-Cell Lymphoma

Altered T-cell subset repertoire affects treatment outcome of patients with myelofibrosis

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