Clinical Signification of Intratumoural Cd8+cd25+ Regulatory T- (Treg) Cells in Prostate Carcinoma

Comperat, E.; Egevald, L.; Rouprêt, M.; Vaessen, C.; Valdman, Alexander; Jonmarker, Sara; Richard, F.; Capron, Frédérique; Charlotte, F.

doi:10.1016/s1569-9056(08)60723-x

Cited by 6 publications

(6 citation statements)

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“…As Treg numbers were unchanged, the CD8 effector:Treg ratio was similarly increased. Notably, the CD8:Treg ratio has been shown to correlate with favorable prognosis in prostate cancer [ 31 , 32 ]. Cxcl9, a widely reported T-cell chemoattractant, was down-regulated in Klf4(f/f);Lys-Cre mice and our data did not reveal up-regulation of genes involved in T cell chemotaxis.…”

Section: Discussionmentioning

confidence: 99%

Absence of myeloid Klf4 reduces prostate cancer growth with pro-atherosclerotic activation of tumor myeloid cells and infiltration of CD8 T cells

et al. 2018

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The microenvironment of prostate cancer often includes abundant tumor-associated macrophages (TAMs), with their acquisition of an M2 phenotype correlating with local aggressiveness and metastasis. Tumor-derived M-CSF contributes to TAM M2 polarization, and M-CSF receptor inhibition slows prostate cancer growth in model systems. As additional cytokines can direct TAM M2 polarization, targeting downstream transcription factors could avoid resistance. Klf4 and C/EBPβ each contribute to monocyte development, and reduced expression of macrophage Klf4 or C/EBPβ favors their adoption of a pro-inflammatory M1 state. We find that a Hi-Myc C57BL/6 prostate cancer line grows more slowly in syngeneic Klf4(f/f);Lys-Cre compared with Klf4(f/f) mice when inoculated subcutaneously, but grows equally rapidly in C/EBPβ(f/f);Lys-Cre and C/EBPβ(f/f) hosts. In the absence of myeloid Klf4, TAMs have reduced expression of surface mannose receptor and Fizz1 mRNA, both M2 markers. Global gene expression analysis further revealed activation of pro-inflammatory, pro-atherosclerotic pathways. Analysis of tumor-infiltrating lymphocytes (TILs) demonstrated markedly increased activated CD8 T cell numbers, and CD8 T cell depletion obviated the inhibitory effect of myeloid Klf4 deletion on prostate cancer growth. These findings suggest that reducing expression or activity of the Klf4 transcription factor in tumor myeloid cells may contribute to prostate cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Absence of myeloid Klf4 reduces prostate cancer growth with pro-atherosclerotic activation of tumor myeloid cells and infiltration of CD8 T cells

et al. 2018

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“…Ness et al showed that the negative prognostic effect may be mediated primarily through CD8 + lymphocytes rather than the overall density of T lymphocytes as measured by CD3 positivity [283], while Davidsson et al attributed the poor prognostic effect to T regs in the prostate cancer microenvironment [284]. Others have reported a correlation between FOXP3 + TILs in prostate cancer and biochemical recurrence [285], though Vesalainen et al reported that tumors with dense TILs were associated with higher survival rates than tumors with absent or decreased TILs [286]. In a recent study it was found that higher CD8 + and lower PD-1 + TIL scores correlated to a longer biochemical-recurrence free survival in patients subjected to salvage radiotherapy after biochemical relapse [287].…”

Section: Tils In Genitourinary Carcinomasmentioning

confidence: 99%

Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non–Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors

Hendry

Salgado

Gevaert

et al. 2017

Advances in Anatomic Pathology

569

366

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Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. In part 2 of this review, we discuss the available evidence for the prognostic and predictive value of TILs in common solid tumors, including carcinomas of the lung, gastrointestinal tract, genitourinary system, gynecological system, and head and neck, as well as primary brain tumors, mesothelioma and melanoma. The particularities and different emphases in TIL assessment in different tumor types are discussed. The standardized methodology we propose can be adapted to different tumor types and may be used as a standard against which other approaches can be compared. Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.

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“…We have previously demonstrated that the prevalence of CD4 + CD25 high T cells in the prostate was higher in the tumor than in benign tissue from the same prostate (17, 18). Furthermore, the frequency of CD4 + CD25 high T cells in peripheral blood was significantly higher in PC patients than in normal donors (17).…”

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confidence: 99%

Distribution of Foxp3‐, CD4‐ and CD8‐positive lymphocytic cells in benign and malignant prostate tissue

Valdman

Jaraj

Compérat

et al. 2010

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Foxp3 is a transcription factor that inhibits antitumor immune response and is expressed in regulatory T cells (Tregs). High levels of Tregs have been reported in several human cancers. This study investigates the distribution of cells positive for Foxp3, CD4 and CD8 in benign prostatic tissues and prostatic carcinoma. Tissue microarrays were constructed from radical prostatectomy specimens of 36 patients. From each patient, six cores were taken: two cores from cancer, one from benign tissue of each of the peripheral (PZ), transition (TZ) and central zones (CZ) and one from atrophy. Foxp3-, CD4- and CD8-positive cells were more common in cancer than in non-atrophic benign tissue (p < 0.01) and more common in atrophy than in non-atrophic PZ, but did not differ significantly between cancer and atrophy. Cells positive for Foxp3 and CD4 were less prevalent in CZ than in PZ and TZ. Tregs infiltrate more in prostate cancer (PC) than in benign tissue. Their presence in atrophy may have relevance for the hypothesis on atrophy as a potential precursor lesion of PC. CZ has the lowest Treg levels, and a possible role for the low rate of cancer in this zone remains to be investigated.

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Clinical Signification of Intratumoural Cd8+cd25+ Regulatory T- (Treg) Cells in Prostate Carcinoma

Cited by 6 publications

References 0 publications

Absence of myeloid Klf4 reduces prostate cancer growth with pro-atherosclerotic activation of tumor myeloid cells and infiltration of CD8 T cells

Absence of myeloid Klf4 reduces prostate cancer growth with pro-atherosclerotic activation of tumor myeloid cells and infiltration of CD8 T cells

Distribution of Foxp3‐, CD4‐ and CD8‐positive lymphocytic cells in benign and malignant prostate tissue

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