Immune profiles of CD4+ lymphocyte subsets in breast cancer tumor draining lymph nodes

Faghih, Zahra; Erfani, Nasrollah; Haghshenas, Mohammad Reza; Safaei, Akbar; Talei, Abdolrasoul; Ghaderi, Abbas

doi:10.1016/j.imlet.2013.11.021

Cited by 68 publications

(65 citation statements)

References 53 publications

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“…However, it is unclear what triggers macrophage polarization during postpartum involution toward an M2-like phenotype. Further, cytokines produced by M2-like macrophages (e.g., IL-4, IL-10, IL-13, TGF-β1, and EGF) (18)(19)(20)(21) are associated with increased breast cancer malignancy (22)(23)(24)(25). It should be noted that these cytokines, which are involved in wound healing and immune suppression, are produced abundantly during postpartum involution to support mammary remodeling (26)(27)(28)(29), consistent with their potential involvement in ppBC progression.…”

Section: Introductionmentioning

confidence: 85%

“…Results from the present study establish a causal relationship between the tissue remodeling events of physiological postpartum involution and the increased metastasis of postpartum mammary tumors. Both scenarios are characterized by a transient widespread wave of cell death, efferocytosis, M2 macrophage polarization, and production of key wound-healing cytokines, of which the latter 2 correlate with advanced disease and reduced DFS in breast cancer patients (16,24,25,43).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Efferocytosis produces a prometastatic landscape during postpartum mammary gland involution

Stanford¹,

Young²,

Hicks³

et al. 2014

J. Clin. Invest.

129

144

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qRT-PCR. Whole-tumor RNA was harvested with an RNeasy kit (QIAGEN), and cDNA was synthesized (High Capacity; Applied Biosystems) and amplified using the murine cDNA-specific primers (Integrated DNA Technologies) listed in Supplemental Methods, along with SYBR Green Supermix (Bio-Rad). The following primers were used: MRC1 (forward: 5′ CCCTCAGCAAGCGATGTGC 3′; reverse: 5′-GGATACTTGCCAGGT CCCCA-3′); iNOS (forward: 5′-GGAGCATCCCAAGTACGAGTGG-3′; reverse: 5′-CGGCC-CACTTCCTCCAG); IL10 (forward: 5′-GGCGCTGTCATC-GATTTCTCC; reverse: 5′-GGCCTTGTAGACACCTTGGTC); Tgfb1 (forward: 5′-CGCAACAACGCCATCTATGAG; reverse: 5′-CGG-GACAGCAATGGGGGTTC); IL4 (forward: 5′-GGTCACAGGAGAAGG-GACG; reverse: 5′-GCGAAGCACCTTGGAAGCC);, IL12b (forward: 5′-GGAGTGGGATGTGTCCTCAG; reverse: 5′-CGGGAGTCCAGTC-CACCTCT); CCL3 (forward: 5′-CCACTGCCCTTGCTGTTCTTCTCT; reverse: 5′-GGGTGTCAGCTCCATATGGCG); and Rplp0 (forward: 5′-TCCTATAAAAGGCACACGCGGGC; reverse: 5′-AGACGATGT-CACTCCAACGAGGACG). Target To generate apoptotic MCF7, cells were treated in suspension with 1 μm BKM120 plus 2 μm ABT-263 (both inhibitors from Selleck Chemicals) for 4 hours, washed 5 times with PBS to remove residual drug, and used directly for efferocytosis assays or for annexin V staining. For efferocytosis coculture assays, Raw264.7-GFP cells (10 4 /well) and PyVmT or MCF7 cells (72 hours after infection with Ad.mCherry and Ad.HS-V-TK) were seeded together in a monolayer in 24-well plates in 2% FBS and cultured for 24 hours prior to the addition PBS or gancyclovir. Cells were imaged at 8, 16, and 32 h after addition of gancyclovir. Cells were collected and counted under fluorescence after 32 hours of coculture. In some experiments, Raw264.7-GFP cells (10 4 / well) were seeded in a monolayer in 24-well plates and cultured for 24 hours prior to the addition of 10 3 live MCF7-mCherry or 10 3 dead MCF7-mCherry cells in serum-free media. Where indicated in the figures, BMS-777607 (1 μm) or a neutralizing goat anti-mouse MerTK antibody (AF591, 25 μg/ml; R&D Systems)(44) was added 2 hours prior to the addition of gancyclovir or 2 hours prior to the addition of dead MCF7 cells to macrophage monolayers. Live and dead MCF7 cells were similarly seeded without Raw264.7 cells as single cultures. Media were collected after 16 hours of coculture, passed through a 0.2-μm filter, and used neat (250 μl) to quantify murine IL-10 and IL-4 by ELISA (BioLegend) according to the manufacturer's protocol. Total remaining cells were collected after 16 hours of coculture, lysed, and RNA was collected using an RNeasy kit (QIAGEN). MethodsMice. All mice were inbred on an FVB background for more than 10 generations. WT FVB, MMTV PyVmT and MerTK -/-mice (67), originally referred to as Mer KD , were purchased from The Jackson Laboratory. Mice were genotyped by PCR of genomic DNA as previously described(30). Female virgin mice were randomized into 2 groups: (a) 1 group that remained virgin, and (b) 1 group that was bred from 42 to 44 days of age with WT male mice. Pregnancies were timed according to identification of a va...

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Section: Introductionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Efferocytosis produces a prometastatic landscape during postpartum mammary gland involution

Stanford¹,

Young²,

Hicks³

et al. 2014

J. Clin. Invest.

129

144

View full text Add to dashboard Cite

show abstract

“…These cells are characterized by interferon gamma (IFN-γ) production, which is crucial for the induction and maintenance of antitumour CD8 + T cells [37,38]. CD4 + Th1 cells can also exert antitumour activity that is independent of CD8 + T cells by recruiting and activating innate immune cells, such as NK and macrophages [36].…”

Section: Composition Of Tils In Breast Cancermentioning

confidence: 99%

Tumour-Infiltrating Lymphocytes (TILs) in Breast Cancer: a Predictive or a Prognostic Marker?

Dushyanthen

Savas

Willard-Gallo

et al. 2015

Curr Breast Cancer Rep

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Breast cancer has not been considered as an immunogenic solid cancer type; however, recent studies demonstrate evidence of significant prognostic information that can be derived from immune cell infiltration via tumourinfiltrating lymphocytes (TILs) in patient tumours. The presence of TILs has been associated with increased response rates to cytotoxic chemotherapy as well as targeted therapies, leading to improved disease-free and overall survival in certain breast cancer subtypes. Accordingly, experts have developed a standardized methodology for evaluating TILs within clinical specimens in histopathological practice. An overview of a newly established practical guideline for TIL evaluation in breast cancer is described in this paper. Furthermore, this review discusses the predictive and prognostic significance of TILs, highlighting recent evidence linking TILs to prognosis in breast cancer. In addition, it summarizes the most current understanding of TIL composition as well as mechanisms of immunity generation and suppression. Overall, the current literature demonstrates that TILs are proving to be a promising target for the treatment of immunogenic breast cancers.

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“…The Th cells were divided into several subsets including Th1, Th2, and regulatory T (Treg) cells which release different cytokines [6]. The Th1-related cytokines such as interferon gamma (IFN-γ) and TNF-α increase immune responses to tumor cells, leading to tumor regression, whereas the Th2-related cytokines (such as interleukin (IL)-4 and IL-10) and Tregrelated cytokines (TGF-β and IL-10) reduce the immune responses to tumors [7,8].…”

Section: Introductionmentioning

confidence: 99%

Higher circulating levels of chemokine CCL22 in patients with breast cancer: evaluation of the influences of tumor stage and chemokine gene polymorphism

et al. 2014

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The receptor for CCL22 is named CCR4 that preferentially is expressed on the regulatory T cells (Treg), and accordingly, CCL22 acts as a chemoattractant for the intratumoral Treg migration. The aim of this study was to evaluate the serum CCL22 levels and a single nucleotide polymorphism (SNP) in chemokine gene, [2030 G/C (rs223818)], in patients with breast cancer. Blood samples were collected from 100 women with breast cancer before receiving chemotherapy, radiotherapy, or immunotherapy and 100 age-matched healthy women as a control group. The serum CCL22 levels were measured by ELISA. The DNA extracted and the SNP rs223818 determined by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique. The mean serum CCL22 levels in patients with breast cancer (2398.5 ± 123 Pg/mL) was significantly higher in comparison to healthy control group (974.2 ± 39.9 Pg/mL; P < 0.001). According to the tumor stages, the mean serum levels of CCL22 were 999.8 ± 85.0 Pg/mL in stage I, 1718.8 ± 82.3 Pg/mL in stage II, 2846.8 ± 118.0 Pg/mL in stage III, and 3954.5 ± 245.2 Pg/mL in stage IV. There was significant difference between tumor stages regarding the serum CCL22 levels (P < 0.001). In patients with breast cancer, the frequencies of CC genotype (63%) and C allele (79%) at rs223818 were significantly higher as compared to healthy controls (31 and 52%, respectively; P < 0.001). In both patients and control groups, the mean serum levels of CCL22 in subjects with CC genotype or C allele at rs223818 were also significantly higher as compared to subjects with GG genotype or G allele (P < 0.001). Higher serum CCL22 levels were observed in patients with breast cancer that is increased with advanced stages. These findings represent that the CCL22 may contribute in tumor development. The CC genotype and C allele at rs223818 were more frequent in breast cancer patients. The serum CCL22 levels were affected by genetic variations at SNP rs223818. Accordingly, SNP rs223818 may play a role in the susceptibility to breast cancer.

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Immune profiles of CD4+ lymphocyte subsets in breast cancer tumor draining lymph nodes

Cited by 68 publications

References 53 publications

Efferocytosis produces a prometastatic landscape during postpartum mammary gland involution

Efferocytosis produces a prometastatic landscape during postpartum mammary gland involution

Tumour-Infiltrating Lymphocytes (TILs) in Breast Cancer: a Predictive or a Prognostic Marker?

Higher circulating levels of chemokine CCL22 in patients with breast cancer: evaluation of the influences of tumor stage and chemokine gene polymorphism

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