Clinicopathological Correlates of γδ T Cell Infiltration in Triple-Negative Breast Cancer

Boissière, Florence; Chabab, Ghita; Mollévi, Caroline; Guiu, Séverine; Lopez-Crapez, Evelyne; Ramos, Jeanne; Bonnefoy, Nathalie; Lafont, Virginie; Jacot, William

doi:10.3390/cancers13040765

Cited by 17 publications

(14 citation statements)

References 68 publications

(111 reference statements)

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“…In order to study the role of CXCR2 and its possible link with immune infiltration in TNBC patients, we analyzed the densities of CD11b (a marker of granulocytes), CD66b (a marker of neutrophils) and CXCR2-positive cells on a cohort of 290 samples from patients with TNBCs that we had previously characterized for both their phenotypic characteristics and their immune microenvironment [ 37 , 38 ]. The main characteristics of the studied population are described in Table 1 and are consistent with the classical characteristics of TNBCs (for further details, refer to Materials and Methods).…”

Section: Resultsmentioning

confidence: 99%

“…CD11b, CD66b and CXCR2 expression was analyzed by immunohistochemistry of serial sections from the same TMA blocks used in our previous studies [ 7 , 36 , 37 , 38 ]. For this study, we used anti-CD11b rabbit monoclonal Ab (clone EP45 at 1/400, BioSB, Santa Barbara, CA, USA), anti-CD66b mouse monoclonal (clone 80H3 at 1/200, BioRad, Marnes-la-Coquette, France) and the recently validated anti-CXCR2 mouse monoclonal antibody (clone E-2 at 1/500, Santa Cruz Technology, Dallas, TX, USA) as previously described [ 33 ].…”

Section: Methodsmentioning

confidence: 99%

“…The rabbit monoclonal SP142 antibody (Ventana Medical Systems, Tucson, AZ, USA) was used for PD-L1 detection. The detailed IHC procedures of other IHC markers used in this study (ER, PR, HER2, EGFR, CK5/6, AR, FOXA1, CD3, CD8, PD-L1 and PD1) and retrieved from other previously published studies are available in the corresponding publications [ 7 , 36 , 37 , 38 ].…”

Section: Methodsmentioning

confidence: 99%

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CXCR2 Levels Correlate with Immune Infiltration and a Better Prognosis of Triple-Negative Breast Cancers

Boissière

Jacot

Massol

et al. 2021

Cancers

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Chemokines and their receptors are key players in breast cancer progression and outcome. Previous studies have shown that the chemokine receptor CXCR2 was expressed at higher levels by cells of the tumor microenvironment in triple-negative breast cancers (TNBCs). The aim of this study was to focus our attention on a retrospective cohort of 290 TNBC cases and analyze the involvement of CXCR2, CD11b (a marker of granulocytes) and CD66b (a marker of neutrophils) and their link with immune infiltration and immune checkpoint markers. We report that high densities of CXCR2-, CD11b- and CD66b-positive cells were associated with high-grade tumors. Moreover, molecular apocrine TNBCs, defined here as tumors that express both AR and FOXA1 biomarkers, exhibited low levels of CXCR2 and CD11b. High CXCR2 and CD11b levels were correlated with elevated density of tumor-infiltrating lymphocytes (TILs), CD8+ cytotoxic lymphocytes, expression of PD-L1 by tumor and stromal cells and of PD-1 by stromal cells. On the other hand, CD66b levels were associated only with CD8+, stromal PD-L1 and PD-1 expression. In univariate analysis, low levels of CXCR2 were correlated with poor OS and RFS. In multivariate analysis, low levels of CXCR2 were associated with poor OS. Finally, in TNBC treated with adjuvant chemotherapy, CXCR2 density was associated with longer RFS. Overall, our data highlight the potential beneficial association of high levels of CXCR2 with a subgroup of TNBC patients characterized by a better prognosis.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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CXCR2 Levels Correlate with Immune Infiltration and a Better Prognosis of Triple-Negative Breast Cancers

Boissière

Jacot

Massol

et al. 2021

Cancers

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“…In human solid cancers, γδ tumour-infiltrating lymphocytes (TILs) have been proposed by many studies to be relevant prognostic factors; however, there appear to be differences in their anti-tumour functions across different solid cancer types. Notably, their tumour infiltration and cytolytic activity have been linked with a beneficial role for patient outcome in gastric cancer [ 121 , 122 ], hepatocellular carcinoma [ 68 ], ovarian cancer [ 123 ], colorectal cancer [ 124 , 125 ], renal cell carcinoma [ 126 , 127 ], glioblastoma [ 128 ] and triple-negative breast cancer [ 129 , 130 , 131 ]. On the other hand, they were also reported to have a negative impact on prognosis in ovarian cancer [ 37 ] and oral cancer [ 42 ], and conflicting studies also found them to positively correlate with pathogenesis in colon cancer [ 132 ] and breast cancer [ 133 , 134 ].…”

Section: Anti-tumour Functions Of γδ T Cellsmentioning

confidence: 99%

The Diverse Roles of γδ T Cells in Cancer: From Rapid Immunity to Aggressive Lymphoma

Schönefeldt

Wais

Herling

et al. 2021

Cancers

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γδ T cells are unique players in shaping immune responses, lying at the intersection between innate and adaptive immunity. Unlike conventional αβ T cells, γδ T cells largely populate non-lymphoid peripheral tissues, demonstrating tissue specificity, and they respond to ligands in an MHC-independent manner. γδ T cells display rapid activation and effector functions, with a capacity for cytotoxic anti-tumour responses and production of inflammatory cytokines such as IFN-γ or IL-17. Their rapid cytotoxic nature makes them attractive cells for use in anti-cancer immunotherapies. However, upon transformation, γδ T cells can give rise to highly aggressive lymphomas. These rare malignancies often display poor patient survival, and no curative therapies exist. In this review, we discuss the diverse roles of γδ T cells in immune surveillance and response, with a particular focus on cancer immunity. We summarise the intriguing dichotomy between pro- and anti-tumour functions of γδ T cells in solid and haematological cancers, highlighting the key subsets involved. Finally, we discuss potential drivers of γδ T-cell transformation, summarising the main γδ T-cell lymphoma/leukaemia entities, their clinical features, recent advances in mapping their molecular and genomic landscapes, current treatment strategies and potential future targeting options.

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“… 48 Similar to our results, a recent study found that, in triple negative breast cancer, PIK3CA mutations were not associated with the density of tumor-infiltrating lymphocytes. 49 However, other studies seem to highlight an association between PI3K/Akt activation and immune suppression in breast, prostate, and bladder cancers. 50 - 52 Further research should be performed to better understand these dynamics in glioma.…”

Section: Discussionmentioning

confidence: 99%

PIK3CA Mutations in Diffuse Gliomas: An Update on Molecular Stratification, Prognosis, Recurrence, and Aggressiveness

Brito¹,

Tomás²,

Azevedo

et al. 2022

Clin Med Insights Oncol

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Introduction: PIK3CA is one of the most mutated oncogenes in solid tumors. In breast cancer (ER-positive, HER2-negative), these events represent a predictive biomarker of response to alpelisib. In glioblastomas (GBM), PIK3CA mutations were described as early constitutive events. Here, we investigated PIK3CA mutational profile across glioma molecular subgroups and its relevance during glioma recurrence. Furthermore, PIK3CA mutations’ effect in PI3K pathway, prognosis, and response to therapy was also explored. Material and Methods: Exons 10 and 21 of PIK3CA mutations were evaluated in 394 gliomas and 19 glioma recurrences from Instituto Português de Oncologia Lisboa Francisco Gentil (IPOLFG) and compared with The Cancer Genome Atlas (TCGA) data. TIMER2.0 and NetMHCpan4.1 were used to assess the immune-microenvironment contribution. Results: PIK3CA mutations were identified among all glioma subgroups, although with no impact on their stratification or prognosis. In both cohorts (IPOLFG and TCGA), PIK3CA mutation frequencies in IDH-mutant and IDH-wild-type GBM were similar (IPOLFG: 9% and 3%; TCGA: 8% and 2%). These mutations were not mutually exclusive with PTEN deletion and EGFR amplification. Despite their reduced frequency, we discovered PIK3CA mutations were maintained during glioma recurrence regardless of administered therapies. The immune microenvironment might not contribute to this phenotype as PIK3CA mutations did not influence immune cell infiltration. Conclusions: Despite the absence of a predominant effect in glioma stratification, PIK3CA mutations were maintained during glioma recurrence, possibly contributing to glioma cell survival, representing promising therapeutic targets in recurrent glioma. Nevertheless, understanding the potential synergistic effects between PIK3CA mutations, PTEN deletion, and EGFR amplification is pivotal to targeted therapies’ efficiency.

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Clinicopathological Correlates of γδ T Cell Infiltration in Triple-Negative Breast Cancer

Cited by 17 publications

References 68 publications

CXCR2 Levels Correlate with Immune Infiltration and a Better Prognosis of Triple-Negative Breast Cancers

CXCR2 Levels Correlate with Immune Infiltration and a Better Prognosis of Triple-Negative Breast Cancers

The Diverse Roles of γδ T Cells in Cancer: From Rapid Immunity to Aggressive Lymphoma

PIK3CA Mutations in Diffuse Gliomas: An Update on Molecular Stratification, Prognosis, Recurrence, and Aggressiveness

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