Peripheral T cell responses to tumour antigens are associated with molecular, immunogenetic and cellular features of breast cancer patients

Janssen, Nicole; Fortis, Sotirios P.; Speigl, Lisa; Haritos, Christoforos; Sotiriadou, Nectaria N.; Sofopoulos, Michael; Arnogiannaki, Niki; Stavropoulos-Giokas, Catherine; Dinou, Amalia; Perez, Sonia A.; Pawelec, Graham; Baxevanis, Constantin N.; Shipp, Christopher

doi:10.1007/s10549-016-4037-z

Cited by 7 publications

(2 citation statements)

References 30 publications

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“…Immunostaining, with CD8 (SP16, 1:80; Thermo Scientific, Waltham, MA, USA), CD163 (10D6, 1:400; Biocare) and FoxP3 (236A/E7, 1:100; Abcam), was performed for all patients using the Leica Bond III automation (Leica Biosystems, Nußloch, Germany) and Leica detection kit (Leica Biosystems, Newcastle, UK), as previously described. Quantification of the infiltrating cells/mm 2 was performed, as described in [ 28 , 29 , 30 ]. Representative staining of the tumor samples for the CD8+, FoxP3+ and CD163+ cells in the tumor center and invasive margin are shown in Figure 1 .…”

Section: Methodsmentioning

confidence: 99%

Association between Intratumoral CD8+ T Cells with FoxP3+ and CD163+ Cells: A Potential Immune Intrinsic Negative Feedback Mechanism for Acquired Immune Resistance

Fortis

Sofopoulos

Goulielmaki

et al. 2022

Cancers

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Acquired immune resistance (AIR) describes a situation in which cancer patients who initially responded clinically to immunotherapies, after a certain period of time, progress with their disease. Considering that AIR represents a feedback response of the tumor against the immune attack generated during the course of immunotherapies, it is conceivable that AIR may also occur before treatment initiation as a mechanism to escape endogenous adaptive antitumor immunity (EAAI). In the present study, we assessed the EAAI in paraffin-embedded breast primary tumor tissue samples and drew correlations with the clinical outcomes. In particular, we analyzed densities of CD8+ cells as elements mediating antitumor cytotoxicity, and of CD163+ and FoxP3+ cells as suppressor elements. We found a direct correlation between the densities of CD8+ cells and of CD163+ and/or FoxP3+ cells in the vast majority of patients’ tumors. Importantly, the vast majority of patients whose tumors were overpopulated by CD8+ cells developed AIR, which was characterized by high intratumoral CD163+ and/or FoxP3+ cell densities and reduced overall survival (OS). We also showed that AIR depends on the levels of CD8+ cell-ratios in the tumor center to the invasive margin. Our data suggest that tumors develop AIR only when under a robust endogenous immune pressure.

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Section: Methodsmentioning

confidence: 99%

Association between Intratumoral CD8+ T Cells with FoxP3+ and CD163+ Cells: A Potential Immune Intrinsic Negative Feedback Mechanism for Acquired Immune Resistance

Fortis

Sofopoulos

Goulielmaki

et al. 2022

Cancers

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“…The CD4 + /CD8 + ratio reflects a dynamic balance under normal conditions ( 4 ). The proportion of CD8 + cells increases, while the proportions of CD3 + , CD4 + and CD19 + cells decrease in the peripheral blood of tumor patients ( 5 , 6 ). In recent years, γδ T cells have been attracting increasing attention due to their unique histological distribution and immunological characteristics, and their key anti-infection and antitumor properties.…”

Section: Introductionmentioning

confidence: 99%

Association between αβ and γδ T‑cell subsets and clinicopathological characteristics in patients with breast cancer

et al. 2020

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The aim of the present study was to discuss the effect of surgery on the T-lymphocyte subsets of patients with breast cancer (BC) and investigate the association between peripheral blood αβ and γδ T-cell counts and the clinicopathological characteristics of BC. The CD3 + , CD4 + , CD8 + and γδ T-cell subsets in the peripheral blood of healthy volunteers and Patients with BC before and after surgery were determined using flow cytometry. The association between αβ and γδ T-cell counts in the peripheral blood and clinicopathological characteristics was analyzed by comparing the differences in the αβ and γδ T-cell counts in the peripheral blood of Patients with BC before and after surgery with those of healthy volunteers and combining with clinicopathological data. The CD3 + , CD4 + and γδ T-cell counts in the peripheral blood of Patients with BC were lower compared with those in healthy volunteers (P=0.0077, 0.0116 and 0.0003, respectively), whereas the number of CD8 + cells was higher (P=0.0241). The CD3 + , CD4 + and γδ T-cell counts and the CD4 + /CD8 + ratio after surgery were significantly higher compared with those before surgery (P=0.0109, 0.0031, 0.0165 and 0.018, respectively). There was no significant difference between the number of CD8 + cells before and after surgery (P=0.0053), but the number of CD8 + cells was higher in healthy volunteers compared with that in Patients with BC (P<0.05). Moreover, the CD3 + cell number was higher in patients with TNM stage II/III compared with those with TNM stage I disease (P=0.187 and 0.022, respectively), and the peripheral blood CD4 + /CD8 + ratio and number of γδ T cells were lower in stage III compared with stage I Patients with BC (P=0.0065 and 0.0176, respectively). Histological grading demonstrated that the CD4 + /CD8 + ratio and number of γδ T cells in patients with stage III BC were lower compared with those with stage I BC (P=0.02 and 0.0128, respectively). The γδ T-cell count in patients with luminal A and B subtypes was significantly higher compared with that in patients with basal-like subtype (P=0.004 and 0.0104, respectively). The CD3 + , CD4 + and γδ T-cell counts were significantly lower in patients with lymph node (LN) metastasis compared with those without LN metastasis, and the CD8 + cell number was lower in patients without LN metastasis compared with that in patients with >10 LN metastases (P=0.0086, 0.0000 and 0.00468, respectively). The CD8 + cell count in patients without LN metastasis was lower compared with that in patients with 4–9 and >10 LN metastases (P=0.0...

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Expansion and Determination of Antigen-Reactive T Cells by Flow Cytometry

Martens

Pawelec

Shipp

2019

Methods in Molecular Biology

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Peripheral T cell responses to tumour antigens are associated with molecular, immunogenetic and cellular features of breast cancer patients

Abstract: This study therefore defines composite immune profiles that identify patients responding to TAAs which may allow better personalisation of cancer therapies.

Cited by 7 publications

References 30 publications

Association between Intratumoral CD8+ T Cells with FoxP3+ and CD163+ Cells: A Potential Immune Intrinsic Negative Feedback Mechanism for Acquired Immune Resistance

Association between Intratumoral CD8+ T Cells with FoxP3+ and CD163+ Cells: A Potential Immune Intrinsic Negative Feedback Mechanism for Acquired Immune Resistance

Association between αβ and γδ T‑cell subsets and clinicopathological characteristics in patients with breast cancer

Expansion and Determination of Antigen-Reactive T Cells by Flow Cytometry

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Peripheral T cell responses to tumour antigens are associated with molecular, immunogenetic and cellular features of breast cancer patients

Abstract: This study therefore defines composite immune profiles that identify patients responding to TAAs which may allow better personalisation of cancer therapies.

Cited by 7 publications

References 30 publications

Association between Intratumoral CD8+ T Cells with FoxP3+ and CD163+ Cells: A Potential Immune Intrinsic Negative Feedback Mechanism for Acquired Immune Resistance

Association between Intratumoral CD8+ T Cells with FoxP3+ and CD163+ Cells: A Potential Immune Intrinsic Negative Feedback Mechanism for Acquired Immune Resistance

Association between &alpha;&beta; and &gamma;&delta; T‑cell subsets and clinicopathological characteristics in patients with breast cancer

Expansion and Determination of Antigen-Reactive T Cells by Flow Cytometry

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Association between αβ and γδ T‑cell subsets and clinicopathological characteristics in patients with breast cancer