Patients with metastatic breast cancer leading to CD4+ T cell lymphopaenia have poor outcome

Trédan, Olivier; Manuel, Manuarii; Clapisson, Gilles; Bachelot, Thomas; Chabaud, Sylvie; Bardin-Dit-Courageot, Christine; Rigal, Chantal; Biota, Cathy; Bajard, Agathe; Pasqual, Nicolas; Blay, Jean‐Yves; Caux, Christophe; Ménétrier‐Caux, Christine

doi:10.1016/j.ejca.2012.11.028

Cited by 50 publications

(54 citation statements)

References 35 publications

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“…The present study is, to our knowledge, the first to assess the relationship of peripheral CCL22 levels in glioma survival, which can be more easily applied as a routine assay for prognosis than most tumor markers. Our findings are consistent with two cohort studies on metastatic breast cancer showing that low CCL22 levels were associated both with low CD4 counts and reduced overall survival . This raises the possibility that in the context of radiochemotherapy for cancer, CCL22 might be considered an indicator of DC related immune suppression.…”

Section: Discussionsupporting

confidence: 91%

“…Our findings are consistent with two cohort studies on metastatic breast cancer showing that low CCL22 levels were associated both with low CD4 counts and reduced overall survival. 16 This raises the possibility that in the context of radiochemotherapy for cancer, CCL22 might be considered an indicator of DC related immune suppression. However, the association of low CCL22 and abnormal CD4 counts was not observed in our control group, even though a small number of subjects demonstrated <200 CD4 cells/lL.…”

Section: Discussionmentioning

confidence: 99%

“…Other studies also have reported that low CD4 counts were associated with poorer glioma survival times . More generally, CD4 lymphopenia has been shown to be a grave prognostic indicator in multiple types of cancers . Although the etiology of depressed T cell immunity in glioma is complex; exposures to therapeutic steroids, chemotherapy and ionizing radiation as well as tumor generated immune suppression are thought to be involved .…”

mentioning

confidence: 99%

“…14,15 More generally, CD4 lymphopenia has been shown to be a grave prognostic indicator in multiple types of cancers. [16][17][18][19][20][21] Although the etiology of depressed T cell immunity in glioma is complex; exposures to therapeutic steroids, chemotherapy and ionizing radiation as well as tumor generated immune suppression are thought to be involved. 12,13 One important aspect of glioma related suppression of the immune response is the effect that tumors may have on professional antigen presenting cells (APC) and their crosstalk with T cells.…”

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confidence: 99%

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Serum macrophage-derived chemokine/CCL22 levels are associated with glioma risk, CD4 T cell lymphopenia and survival time

et al. 2015

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Defects in antigen presenting cell function have been implicated in glioma immunosuppression. We measured peripheral CCL22, a dendritic cell/macrophage derived T cell trafficking chemokine, in sera from 1,208 glioma cases and 976 controls to assess whether it might provide a biomarker of glioma risk, survival, and immune dysfunction. Cluster models were used to examine the relationship between CCL22 and glioma risk. Patient survival was assessed using Cox regression models. We also examined the relationship between CCL22 levels and CD4 cell counts, as well as allergy history and IgE levels. CCL22 levels were significantly lower among glioma cases compared to controls (Mean±SEM: 1.23±0.03 ng/mL in cases versus 1.60±0.03 ng/mL in controls, P<0.0001), and this difference remained significant even after controlling for other covariates in the cluster models (highest quartile versus lowest Odds Ratio=0.21, P<0.0001). CD4 cell counts were positively correlated with CCL22 in glioma cases (Spearman r2=0.51, P<0.01) and were significantly lower in cases compared with controls. Higher CCL22 levels were associated with longer survival in all cases combined and in GBM cases (hazard ratioallcases=0.81; 95% CI: 0.72–0.91, P=0.0003). CCL22 levels were not associated with IgE level or self-reported allergies. Circulating CCL22 levels are related to both glioma risk and survival duration independent of age, histology, grade and IDH mutation status. CCL22 should be considered a marker of immune status with potential prognostic value.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Serum macrophage-derived chemokine/CCL22 levels are associated with glioma risk, CD4 T cell lymphopenia and survival time

et al. 2015

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“…16,17 More generally, T cell lymphopenia has been shown to be a grave prognostic indicator in multiple types of cancers. [18][19][20][21][22][23] Recently, digital PCR platforms have been developed that offer advantages over real time qPCR including the capability to obtain absolute quantification without external references and to be highly robust to variations in PCR efficiency, thus improving assay precision. [25][26][27] Digital PCR is based on limiting dilution of a sample into a large number of separate PCR reactions.…”

Section: Introductionmentioning

confidence: 99%

A comparison of DNA methylation specific droplet digital PCR (ddPCR) and real time qPCR with flow cytometry in characterizing human T cells in peripheral blood

et al. 2014

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Quantitating the copy number of demethylated CpG promoter sites of the CD3Z gene can be used to estimate the numbers and proportions of T cells in human blood and tissue. Quantitative methylation specific PCR (qPCR) is useful for studying T cells but requires extensive calibration and is imprecise at low copy numbers. Here we compared the performance of a new digital PCR platform (droplet digital PCR or ddPCR) to qPCR using bisulfite converted DNA from 157 blood specimens obtained from ambulatory care controls and patients with primary glioma. We compared both ddPCR and qPCR with conventional flow cytometry (FACS) evaluation of CD3 positive T cells. Repeated measures on the same blood sample revealed ddPCR to be less variable than qPCR. Both qPCR and ddPCR correlated significantly with FACS evaluation of peripheral blood CD3 counts and CD3/total leukocyte values. However, statistical measures of agreement showed that linear concordance was stronger for ddPCR than for qPCR and the absolute values were closer to FACS for ddPCR. Both qPCR and ddPCR could distinguish clinically significant differences in T cell proportions and performed similarly to FACS. Given the higher precision, greater accuracy, and technical simplicity of ddPCR, this approach appears to be a superior DNA methylation based method than conventional qPCR for the assessment of T cells.

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Predictive and prognostic value of circulating blood lymphocyte subsets in metastatic breast cancer

Yang

Ying

et al. 2019

Cancer Medicine

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The treatment of breast cancer (BC) has improved greatly in recent years, however, the limitations of current therapeutic modalities underscore the need to define new prognostic tools and develop highly targeted therapies. The aims of the present study were to explore the effects of circulating blood lymphocyte subsets on the survival of metastatic breast cancer (MBC) patients and to evaluate their predictive and prognostic value. The clinical data of 482 patients with MBC were retrospectively analyzed, and patients were grouped according to molecular types of BC. The distribution of peripheral blood lymphocyte subsets at the time of first metastasis was examined by flow cytometry, and the distribution of lymphocyte subsets in each group was categorized into ‘‘high or low’’ subgroups using the upper quartile point as the cutoff. The relationship between the distribution of lymphocyte subsets and progression‐free survival (PFS) as well as overall survival (OS) was evaluated in diverse molecular MBCs. In multivariate analysis, CD4+ was a negative independent predictor of PFS (hazard ratio [HR] = 0.538, 95% confidence interval [CI] = 0.313‐0.926, P = 0.025) and CD3+ was a poor independent prognostic factor for OS (HR = 0.437, 95% CI = 0.248‐0.772, P = 0.004) in the human epidermal growth factor receptor 2 (HER2)‐positive group. Neither the CD8+, CD19+, and CD56+ lymphocyte subsets nor the CD4+/CD8+ ratio in peripheral blood was significant predictive or prognostic factors. In conclusion, higher circulating levels of CD4+ and CD3+ at first diagnosis in HER2‐overexpressing MBC were significantly associated with worse survival outcomes. Low levels of plasma CD4+ and CD3+ were associated with increased anti‐HER2 benefit in HER2‐positive MBC. The present results indicate that these factors can be used as predictive and prognostic indicators of the outcome of patients with MBC.

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Patients with metastatic breast cancer leading to CD4+ T cell lymphopaenia have poor outcome

Cited by 50 publications

References 35 publications

Serum macrophage-derived chemokine/CCL22 levels are associated with glioma risk, CD4 T cell lymphopenia and survival time

Serum macrophage-derived chemokine/CCL22 levels are associated with glioma risk, CD4 T cell lymphopenia and survival time

A comparison of DNA methylation specific droplet digital PCR (ddPCR) and real time qPCR with flow cytometry in characterizing human T cells in peripheral blood

Predictive and prognostic value of circulating blood lymphocyte subsets in metastatic breast cancer

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