Distribution, function, and prognostic value of cytotoxic T lymphocytes in follicular lymphoma: a 3-D tissue-imaging study

Laurent, Camille; Müller, Sabina; Do, Catherine; Al-Saati, Talal; Allart, Sophie; Larocca, Luigi Maria; Hohaus, Stefan; Duchez, Sophie; Quillet‐Mary, Anne; Laurent, Guy; Brousset, Pierre; Valitutti, Salvatore

doi:10.1182/blood-2011-04-345777

Cited by 70 publications

(59 citation statements)

References 34 publications

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“…Similar to previous reports, 34 a perifollicular distribution of CD8 + T cells was present in 4 of 6 samples analyzed by IHC. Interestingly, tumors with a perifollicular CD8 + T-cell distribution tended to have a stronger enrichment of oligoclonal T cells in the CD8 compartment, whereas a more polyclonal CD8 + TCR distribution was seen in tumors with a more prominent intrafollicular CD8 + T-cell infiltration.…”

Section: Discussionsupporting

confidence: 77%

Highly clonal regulatory T-cell population in follicular lymphoma – inverse correlation with the diversity of CD8⁺T cells

et al. 2015

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The immune microenvironment in follicular lymphoma (FL) plays an important role in controlling disease characteristics. To characterize the T-cell receptor (TCR) repertoire in follicular lymphoma (FL) tissues, we applied a nextgeneration sequencing platform and deeply sequenced TCR cDNAs of T-cell subset populations present in pretreatment FL biopsy specimens. T regulatory cell (T reg ) TCRs in FL tissues revealed a highly oligoclonal expansion compared to those in control lymph nodes. Furthermore, an inverse correlation was observed between the diversity of T reg and CD8 + TCRs in FL specimens. Interestingly, a tumor from an FL patient, who had not received anticancer treatment for more than 10 years, was found to have missense mutations in the peptide-binding domain of both human leukocyte antigen (HLA) class I and II molecules, which might have presented tumor-specific antigens and enhanced host immune responses. Although further verification is required, our data suggest that the T-cell repertoire is skewed and restricted in FL and support the evolving understanding of the microenvironment in this disease.

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Section: Discussionsupporting

confidence: 77%

Highly clonal regulatory T-cell population in follicular lymphoma – inverse correlation with the diversity of CD8⁺T cells

et al. 2015

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“…For example, immune synapses between malignant B cells and T cells are defective, although CD8 + CTLs have been shown to localize at the follicle border and enter into contact with tumor cells. 27,34 It was also shown that IL-12 secretion by malignant B cells induces T-cell exhaustion (right lower corner of Fig. 1) via expression of TIM3.…”

Section: M2 Polarization Of Macrophagesmentioning

confidence: 99%

“…Finally, although GrzB expression in CTLs was not correlated with risk factors, high GrzB content was correlated with prolonged progression-free survival (PFS) after rituximab-combined chemotherapy. 34 The immune microenvironment plays an important role in FL outcomes, and genes and proteins expressed by infiltrating T cells and macrophages are among the most important predictors of outcome. 31,32,35,36 CD8 + and CD4 + tumorinfiltrating lymphocytes (TILs) in FL were shown to impair the function and suppress the recruitment of critical signaling proteins to the immunologic synapse.…”

Section: Cd8 + T Cellsmentioning

confidence: 99%

Follicular Lymphoma: The Role of the Tumor Microenvironment in Prognosis

Sugimoto

Watanabe

2016

JCEH

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The microenvironment of follicular lymphoma (FL) is composed of tumor-infiltrating CD8 + T cells, follicular regulatory T cells, lymphoma-associated macrophages and mast cells, follicular helper T cells, follicular dendritic cells, and follicular reticular cells, all of which have been reported to have relevance in the prognosis of FL patients. In addition, some of these cells play a role in the histologic transformation of FL. Macrophages contribute to a poor prognosis in FL patients treated in the prerituximab era, but are associated with good prognosis in those treated in the rituximab era. T-cell immunoglobulin and mucin domain protein (TIM) 3 are markers of T-cell exhaustion, and T cells co-expressing programed death 1 (PD1) in peripheral blood and lymph nodes secrete interleukin (IL)-12 in the serum. Serum CXCL9, IL-2 receptor, and IL-1 receptor agonist are associated with shorter survival of FL patients. Agents for manipulation of the microenvironment surrounding FL cells include the immunomodulatory drug lenalidomide, immune check-point inhibitors, and cyclophosphamide prior to rituximab. To battle FL and to improve the outcomes of FL patients, understanding the relationship between neoplastic cells and the various microenvironmental cellular components is crucial for developing therapeutics against the microenvironment.

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“…FL B-cells divert the classical activation of the innate immune system and subvert the function of the adaptive immune response. For example, immune synapses between malignant B cells and T cells are defective, although CD8 + CTLs have been shown to localize at the follicle border and enter into contact with tumor cells (85,86). It was also recently shown that IL-12 secretion by malignant B cells induces T cell exhaustion via expression of TIM3 (87).…”

Section: Figurementioning

confidence: 99%

Pathogenesis of follicular lymphoma

Kridel¹,

Sehn²,

Gascoyne³

2012

J. Clin. Invest.

279

207

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The hallmark t(14;18)(q32;q21) in follicular lymphoma (FL) results in constitutive overexpression of the BCL2 protein, allowing B cells to abrogate the default germinal center apoptotic program. Most tumors are characterized by recurrent secondary genetic alterations including genomic gains, losses, and mutations, some providing a growth advantage, including alterations in MLL2, EPHA7, TNFRSF14, and EZH2. The sequence in which these events occur and how they contribute to progression and ultimately to transformation is unclear. Lastly, crosstalk between neoplastic B cells and non-neoplastic immune and stromal cells in the microenvironment plays an important role in sustaining tumor cell growth, cultivating immune privilege, and promoting transformation.

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Distribution, function, and prognostic value of cytotoxic T lymphocytes in follicular lymphoma: a 3-D tissue-imaging study

Cited by 70 publications

References 34 publications

Highly clonal regulatory T-cell population in follicular lymphoma – inverse correlation with the diversity of CD8⁺T cells

Highly clonal regulatory T-cell population in follicular lymphoma – inverse correlation with the diversity of CD8⁺T cells

Follicular Lymphoma: The Role of the Tumor Microenvironment in Prognosis

Pathogenesis of follicular lymphoma

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Distribution, function, and prognostic value of cytotoxic T lymphocytes in follicular lymphoma: a 3-D tissue-imaging study

Cited by 70 publications

References 34 publications

Highly clonal regulatory T-cell population in follicular lymphoma – inverse correlation with the diversity of CD8+T cells

Highly clonal regulatory T-cell population in follicular lymphoma – inverse correlation with the diversity of CD8+T cells

Follicular Lymphoma: The Role of the Tumor Microenvironment in Prognosis

Pathogenesis of follicular lymphoma

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Product

Resources

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Highly clonal regulatory T-cell population in follicular lymphoma – inverse correlation with the diversity of CD8⁺T cells

Highly clonal regulatory T-cell population in follicular lymphoma – inverse correlation with the diversity of CD8⁺T cells