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Fulltext Construction of single-chain variable fragment antibodies against MCF-7 breast cancer cells

Zuhaida AA, Ali AM, Tamilselvan S, Alitheen NB, Hamid M, Noor AM, et al.

Genet. Mol. Res., 2013;12(4):5547-59.
PMID: 24301925 DOI: 10.4238/2013.November.18.5

A phage display library of single chain variable fragment (scFv) against MCF-7 breast cancer cells was constructed from C3A8 hybridoma cells. RNA from the C3A8 was isolated, cDNA was constructed, and variable heavy and light immunoglobulin chain gene region were amplified using PCR. The variable heavy and light chain gene regions were combined with flexible linker, linked to a pCANTAB 5E phagemid vector and electrophoresed into supE strain of Escherichia coli TG1 cells. Forty-eight clones demonstrated positive binding activity to MCF-7 breast cancer cell membrane fragments and the strongest of 48 clones was selected for analysis. The anti-MCF-7 library evaluated by SfiI and NotI digests demonstrated that anti-MCF-7 scFv antibodies possess individual patterns that should be able to recognize distinct human breast cancer cells. The C3A8 scFv, with an apparent molecular weight of 32 kDa, showed high homology (99%) with single chain antibody against rice stripe virus protein P20. In summary, the anti MCF-7 scFv antibody can be used for pretargeting breast cancer for clinical diagnosis of patients; it also has potential for therapeutic applications.

Matched MeSH terms: Breast Neoplasms/immunology*
Use of complementary and alternative medicine among breast cancer survivors

Saibul N, Shariff ZM, Rahmat A, Sulaiman S, Yaw YH

Asian Pac J Cancer Prev, 2012;13(8):4081-6.
PMID: 23098520

Complementary and alternative medicine (CAM) use is prevalent among individuals with cancer, especially breast cancer survivors. This study was conducted among 394 breast cancer survivors in selected regions of Peninsular Malaysia to identify the pattern and factors associated with CAM use. About 51% of the respondents reported CAM use as complementary treatment. Vitamins (47.2%), spiritual activities (33.2%) and other dietary supplements (30.7%) were the most commonly used CAM therapies. Common reasons for CAM use were to increase the body's ability to perform daily activities (70.9%), enhance immune function (58.3%) and improve emotional well-being (31.7%). Users obtained CAM information mainly from friends and family members (62.5%), physicians (25.0%) and mass media (13.9%). Ethnicity and years of education were significantly associated with CAM use. Although no adverse effects of CAM were reported, breast cancer survivors should discuss their CAM use with health professionals to prevent potential adverse effects of these therapies.

Matched MeSH terms: Breast Neoplasms/immunology
A mouse IgM monoclonal antibody recognizes breast and colon cancer

Bakar AF, Alitheen NB, Keong YS, Hamid M, Ali SA, Ali AM

Hybridoma (Larchmt), 2009 Jun;28(3):199-203.
PMID: 19519247 DOI: 10.1089/hyb.2007.0531

Hybridoma clone C3A8, which is a fusion product between splenic lymphocytes of Balb/c mice immunized with MCF7 breast carcinoma cells and SP2/0 myelomas, was produced and characterized. A stable clone that secreted IgM monoclonal antibody (MAb) with kappa light chain was obtained through limiting dilutions. Cell-ELISA screening, flow cytometry analysis, and immunofluorescence staining revealed that the MAb C3A8 had bound specifically and strongly to MCF7 and HT29 but cross reacted weakly or not on HeLa cell line. The MAb C3A8 reacted positively with paraffin-embedded tissues of human breast and colon cancers but there were no positive reactions on normal tissues. Western blot analysis showed the MAb recognized a 55 kDa protein, which was present in the extract of MCF7 and HT29 cell lines. Our results demonstrated that MAb C3A8 could be used for basic and clinical research of breast and colon cancers.

Matched MeSH terms: Breast Neoplasms/immunology*
Fulltext Autoantibodies to survivin in the sera of patients with infiltrating ductal carcinoma of the breast

Al-Joudi FS, Iskandar ZA

Med J Malaysia, 2006 Aug;61(3):302-6.
PMID: 17240580 MyJurnal

Autoantibodies to survivin have been reported in lung cancers and in gastrointestinal cancers. A few reports have also described a low prevalence of autoantibodies to survivin and at low titres in the sera of breast cancer patients with no implications for their clinical usefulness. This study was designed to re-examine the prevalence and the clinical correlations of autoantibodies to the tumour protein survivin, in the sera of patients with infiltrating ductal carcinoma of the breast using an ELISA assay. In spite of the low prevalence of autoantibodies to survivin (7%, n = 57), their presence was associated with grade III tumours, with tumour sizes exceeding 10cm, with axillary lymph nodal involvement and with metastases. Moreover, all the autoantibody-positive cases were estrogen and progesterone receptors negative. Furthermore, all the autoantibody-positive cases expressed survivin with high scores.

Matched MeSH terms: Breast Neoplasms/immunology*
Effect of palm oil carotene on breast cancer tumorigenicity in nude mice

Nesaretnam K, Radhakrishnan A, Selvaduray KR, Reimann K, Pailoor J, Razak G, et al.

Lipids, 2002 Jun;37(6):557-60.
PMID: 12120953

Biological therapies are new additions to breast cancer treatment. Among biological compounds, beta-carotene has been reported to have immune modulatory effects, in particular, enhancement of natural killer cell activity and tumor necrosis factor-alpha production by macrophages. The objective of this study was to investigate the effect of palm carotene supplementation on the tumorigenicity of MCF-7 human breast cancer cells injected into athymic nude mice and to explore the mechanism by which palm carotenes suppress tumorigenesis. Forty-eight 4-wk-old mice were injected with 1 x 10(6) MCF-7 cells into their mammary fat pad. The experimental group was supplemented with palm carotene whereas the control group was not. Significant differences were observed in tumor incidence (P< 0.001) and tumor surface area and metastasis to lung (P< 0.005) between the two groups. Natural killer (NK) cells and B-lymphocytes in the peripheral blood of carotene-supplemented mice were significantly increased (P < 0.05 and P < 0.001, respectively) compared with controls. These results suggest that palm oil carotene is able to modulate the immune system by increasing peripheral blood NK cells and B-lymphocytes and suppress the growth of MCF-7 human breast cancer cells.

Matched MeSH terms: Breast Neoplasms/immunology
Recent progress in small molecule agents for the targeted therapy of triple-negative breast cancer

Islam R, Lam KW

Eur J Med Chem, 2020 Dec 01;207:112812.
PMID: 32937283 DOI: 10.1016/j.ejmech.2020.112812

Triple-negative breast cancer (TNBC) is the most aggressive type of cancer, with a high risk of death on recurrence. To date, there is a lack of approved targeted agents for the treatment of the disease. Patients with TNBC continue to depend on surgery, chemotherapy, and radiotherapy, all of which have a wide side effect profile. In the present review, we highlight the current progress and exciting developments in the small-molecule targeted therapy for the treatment of TNBC. Finally, we also discuss the prospect of combining targeted therapy and immunotherapy for the effective treatment of TNBC.

Matched MeSH terms: Triple Negative Breast Neoplasms/immunology
Fulltext Metaplastic breast cancers frequently express immune checkpoint markers FOXP3 and PD-L1

Kalaw E, Lim M, Kutasovic JR, Sokolova A, Taege L, Johnstone K, et al.

Br J Cancer, 2020 11;123(11):1665-1672.
PMID: 32939056 DOI: 10.1038/s41416-020-01065-3

BACKGROUND: Metaplastic breast carcinoma encompasses a heterogeneous group of tumours with differentiation into squamous and/or spindle, chondroid, osseous or rhabdoid mesenchymal-looking elements. Emerging immunotherapies targeting Programmed Death Ligand 1 (PD-L1) and immune-suppressing T cells (Tregs) may benefit metaplastic breast cancer patients, which are typically chemo-resistant and do not express hormone therapy targets.
METHODS: We evaluated the immunohistochemical expression of PD-L1 and FOXP3, and the extent of tumour infiltrating lymphocytes (TILs) in a large cohort of metaplastic breast cancers, with survival data.
RESULTS: Metaplastic breast cancers were significantly enriched for PD-L1 positive tumour cells, compared to triple-negative ductal breast cancers (P breast cancers were also significantly enriched for TILs expressing FOXP3, with FOXP3 positive intra-tumoural TILs (iTILs) associated with an adverse prognostic outcome (P = 0.0226). Multivariate analysis identified FOXP3 iTILs expression status as an important independent prognostic factor for patient survival.
CONCLUSIONS: Our findings indicate the clinical significance and prognostic value of FOXP3, PD-1/PD-L1 checkpoint and TILs in metaplastic breast cancer and confirm that a subset of metaplastics may benefit from immune-based therapies.

Matched MeSH terms: Breast Neoplasms/immunology
The Immunomodulatory Potential of Selected Bioactive Plant-Based Compounds in Breast Cancer: A Review

Baraya YS, Wong KK, Yaacob NS

Anticancer Agents Med Chem, 2017;17(6):770-783.
PMID: 27539316 DOI: 10.2174/1871520616666160817111242

Breast cancer has continued to cause high cancer death rates among women worldwide. The use of plants' natural products in breast cancer treatment has received more attention in recent years due to their potentially wider safety margin and the potential to complement conventional chemotherapeutic drugs. Plantbased products have demonstrated anticancer potential through different biological pathways including modulation of the immune system. Immunomodulatory properties of medicinal plants have been shown to mitigate breast cancer cell growth. Different immune cell types participate in this process especially cytotoxic T cells and natural killer cells, and cytokines including chemokines and tumor necrosis factor-α. Medicinal plants such as Glycyrrhiza glabra, Uncaria tomentosa, Camellia sinensis, Panax ginseng, Prunus armenaica (apricot), Allium sativum, Arctium lappa and Curcuma longa were reported to hold strong potential in breast cancer treatment in various parts of the world. Interestingly, research findings have shown that these plants possess bioactive immunomodulators as their main constituents producing the anticancer effects. These immunomodulatory compounds include ajoene, arctigenin, β-carotene, curcumin, epigallocatechin-3-gallate, ginsan, glabridin and quinic acid. In this review, we discussed the ability of these eight immunomodulators in regulating the immune system potentially applicable in breast cancer treatment via anti-inflammatory (curcumin, arctigenin, glabridin and ajoene) and lymphocytes activation (β-carotene, epigallocatechin-3-gallate, quinic acid and ginsan) properties, as well as future research direction in their use for breast cancer treatment.

Matched MeSH terms: Breast Neoplasms/immunology
Time-Lapse 2D Imaging of Phagocytic Activity in M1 Macrophage-4T1 Mouse Mammary Carcinoma Cells in Co-cultures

Zaidi NE, Shazali NAH, Chor ALT, Osman MA, Ibrahim K, Jaoi-Edward M, et al.

J Vis Exp, 2019 12 14.
PMID: 31885381 DOI: 10.3791/60281

Tumor-associated macrophages (TAMs) have been identified as an important component for tumor growth, invasion, metastasis, and resistance to cancer therapies. However, tumor-associated macrophages can be harmful to the tumor depending on the tumor microenvironment and can reversibly alter their phenotypic characteristics by either antagonizing the cytotoxic activity of immune cells or enhancing anti-tumor response. The molecular actions of macrophages and their interactions with tumor cells (e.g., phagocytosis) have not been extensively studied. Therefore, the interaction between immune cells (M1/M2-subtype TAM) and cancer cells in the tumor microenvironment is now a focus of cancer immunotherapy research. In the present study, a live cell coculture model of induced M1 macrophages and mouse mammary 4T1 carcinoma cells was developed to assess the phagocytic activity of macrophages using a time-lapse video feature using phase-contrast, fluorescent, and differential interference contrast (DIC) microscopy. The present method can observe and document multipoint live-cell imaging of phagocytosis. Phagocytosis of 4T1 cells by M1 macrophages can be observed using fluorescent microscopy before staining 4T1 cells with carboxyfluorescein succinimidyl ester (CFSE). The current publication describes how to coculture macrophages and tumor cells in a single imaging dish, polarize M1 macrophages, and record multipoint events of macrophages engulfing 4T1 cells during 13 h of coculture.

Matched MeSH terms: Breast Neoplasms/immunology*
Fulltext Immunomodulatory effects of Newcastle disease virus AF2240 strain on human peripheral blood mononuclear cells

Lam HY, Yusoff K, Yeap SK, Subramani T, Abd-Aziz S, Omar AR, et al.

Int J Med Sci, 2014;11(12):1240-7.
PMID: 25317070 DOI: 10.7150/ijms.8170

Immunotherapy has raised the attention of many scientists because it hold promise to be an attractive therapeutic strategy to treat a number of disorders. In this study, the immunomodulatory effects of low titers of Newcastle disease virus (NDV) AF2240 on human peripheral blood mononuclear cells (PBMC) were analyzed. We evaluated cytokine secretion and PBMC activation by cell proliferation assay, immunophenotyping and enzyme linked immunosorbent assay. The proliferation of the human PBMC was measured to be 28.5% and 36.5% upon treatment with 8 hemaglutinin unit (HAU) and 2 HAU of NDV respectively. Interestingly, the percentage of cells with activating markers CD16 and CD56 were increased significantly. Furthermore, the intracellular perforin and granzyme levels were also increased upon virus infection. Human PBMC treated with NDV titer 8 HAU was found to stimulate the highest level of cytokine production including interferon-γ, interleukin-2 and interleukin-12. The release of these proteins contributes to the antitumor effect of PBMC against MCF-7 breast cancer cells. Based on the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay, activated human PBMC showed high cytolytic efficiency towards human breast tumor cells. In summary, NDV was able to stimulate PBMC proliferation, cytokine secretion and cytolytic activity.

Matched MeSH terms: Breast Neoplasms/immunology
Fulltext scFv antibody: principles and clinical application

Ahmad ZA, Yeap SK, Ali AM, Ho WY, Alitheen NB, Hamid M

Clin. Dev. Immunol., 2012;2012:980250.
PMID: 22474489 DOI: 10.1155/2012/980250

To date, generation of single-chain fragment variable (scFv) has become an established technique used to produce a completely functional antigen-binding fragment in bacterial systems. The advances in antibody engineering have now facilitated a more efficient and generally applicable method to produce Fv fragments. Basically, scFv antibodies produced from phage display can be genetically fused to the marker proteins, such as fluorescent proteins or alkaline phosphatase. These bifunctional proteins having both antigen-binding capacity and marker activity can be obtained from transformed bacteria and used for one-step immunodetection of biological agents. Alternatively, antibody fragments could also be applied in the construction of immunotoxins, therapeutic gene delivery, and anticancer intrabodies for therapeutic purposes. This paper provides an overview of the current studies on the principle, generation, and application of scFv. The potential of scFv in breast cancer research is also discussed in this paper.

Matched MeSH terms: Breast Neoplasms/immunology
Changes in cellular immunity during chemotherapy for primary breast cancer with anthracycline regimens

Wijayahadi N, Haron MR, Stanslas J, Yusuf Z

J Chemother, 2007 Dec;19(6):716-23.
PMID: 18230556

Anthracyclines are the most widely used anticancer agents for breast cancer, of which doxorubicin and epirubicin have been reported to have equal efficacy. Unfortunately, the integrity of the immune system of breast cancer patients is severely affected by chemotherapy. This study compared the effect of combination chemotherapy with epirubicin (5-fluorouracil, epirubicin, cyclophosphamide (FEC)) and doxorubicin (5-fluorouracil, doxorubicin, cyclophosphamide (FDC)) regimens on subsets of the immune cells of patients with primary malignant breast tumors. Our aim was to determine the best regimen that produces the least degree of myelosuppression. Blood from 80 breast cancer patients undergoing chemotherapy (40 FEC and 40 FDC) was taken before chemotherapy and after every cycle (3 weeks) for 6 cycles. Blood was also taken from 40 normal healthy donors who served as normal control. Subsets of lymphocytes T-helper cells (CD3(+)CD4(+)), T-cytotoxic cells (CD3(+) CD8(+)), B-cells (CD19(+) CD20(+)) and NK cells (CD16(+)/CD56(+)CD3(-)) were analyzed by flow cytometry (FacsCalibur, BD) using monoclonal antibodies (Multitest, BD). All patients in the FEC and FDC groups suffered from myelosuppressive side effects. Both regimens led to an increase in the counts of monocytes but decreased polymorphonuclear cells (PMNs) and lymphocytes. Percentages of T-cytotoxic cells and NK cells were increased, but the percentage of B-cells was dramatically decreased. The phagocytic and intracellular killing ability of PMNs were also suppressed (p<0.01). No significant difference was found between the epirubicin-based regimen and doxorubicin-based regimen with regard to numbers of immune cells, percentages of lymphocytes subsets, Th/CTL ratio, engulfment and killing abilities of PMNs. In conclusion, we found that the epirubicin-based regimen is not superior to the doxorubicin-based regimen with respect to their toxicity of the immune cells, Th/CTL ratio and PMN count and functions. Moreover, both FEC and FDC regimens appear to conserve the cell-mediated immunity response needed for fighting against cancer cells.

Matched MeSH terms: Breast Neoplasms/immunology*
Roles of circulating microRNA(s) in human breast cancer

Chong ZX, Yeap SK, Ho WY

Arch Biochem Biophys, 2020 11 30;695:108583.
PMID: 32956633 DOI: 10.1016/j.abb.2020.108583

miRNAs are short non-coding RNA molecules that regulate the expression of mRNA post-transcriptionally. MiRNAs that are secreted into the circulation, also termed circulating miRNAs, have been studied extensively for their roles in diagnosis, treatment and prognosis of human breast cancer. Breast cancer is the most prevalent female cancer and is associated with key cancer hallmarks including sustained proliferation, evasion of apoptosis, increased invasion, enhanced metastases, initation of inflammation, induction of angiogenesis, metabolic derangement and immune dysregulation. This review aimed to explore the relationships between circulating miRNAs and different breast cancer hallmarks. Besides, the advantages, challenges and clinical application of using circulating miRNAs in human breast cancer management were also discussed.

Matched MeSH terms: Breast Neoplasms/immunology
Diacerein-mediated inhibition of IL-6/IL-6R signaling induces apoptotic effects on breast cancer

Bharti R, Dey G, Ojha PK, Rajput S, Jaganathan SK, Sen R, et al.

Oncogene, 2016 Jul 28;35(30):3965-75.
PMID: 26616855 DOI: 10.1038/onc.2015.466

Interleukin-6 (IL-6) signaling network has been implicated in oncogenic transformations making it attractive target for the discovery of novel cancer therapeutics. In this study, potent antiproliferative and apoptotic effect of diacerein were observed against breast cancer. In vitro apoptosis was induced by this drug in breast cancer cells as verified by increased sub-G1 population, LIVE/DEAD assay, cell cytotoxicity and presence of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, as well as downregulation of antiapoptotic proteins Bcl-2 and Bcl-xL and upregulation of apoptotic protein Bax. In addition, apoptosis induction was found to be caspase dependent. Further molecular investigations indicated that diacerein instigated apoptosis was associated with inhibition of IL-6/IL-6R autocrine signaling axis. Suppression of STAT3, MAPK and Akt pathways were also observed as a consequence of diacerein-mediated upstream inhibition of IL-6/IL-6R. Fluorescence study and western blot analysis revealed cytosolic accumulation of STAT3 in diacerein-treated cells. The docking study showed diacerein/IL-6R interaction that was further validated by competitive binding assay and isothermal titration calorimetry. Most interestingly, it was found that diacerein considerably suppressed tumor growth in MDA-MB-231 xenograft model. The in vivo antitumor effect was correlated with decreased proliferation (Ki-67), increased apoptosis (TUNEL) and inhibition of IL-6/IL-6R-mediated STAT3, MAPK and Akt pathway in tumor remnants. Taken together, diacerein offered a novel blueprint for cancer therapy by hampering IL-6/IL-6R/STAT3/MAPK/Akt network.

Matched MeSH terms: Breast Neoplasms/immunology
Generation and characterization of a high-affinity monoclonal antibody for MUC1 measurement in breast cancer

Hamid SS, Cheah SH

Hybridoma (Larchmt), 2011 Apr;30(2):137-43.
PMID: 21529286 DOI: 10.1089/hyb.2010.0091

Breast mucin is secreted by breast tumor cells and serves as a marker for breast cancer. Thus, antibodies against breast mucin will be valuable in the development of immunotherapy and laboratory diagnostic tests. Monoclonal antibodies (MAbs) against breast cancer-associated antigen were generated and characterized. Balb/c mice were immunized with breast cancer-associated antigen CA15-3, and subsequently splenocytes from immunized mice were fused with myeloma cells. After fusion, culture supernatants from hybridomas surviving HAT medium were screened by enzyme-linked immunosorbent assay (ELISA). A total of eight hybridomas producing MAbs against breast cancer showed significant levels of antibody activity against CA15-3. Two selected stable hybridomas were adapted into CELLine CL 350 bioreactors, and the MAbs produced were characterized for their subclass, specificity, and affinity. The MAbs were of high specificity and affinity as shown by ELISA. The MAbs produced may represent a powerful tool and are considered promising reagents for use in diagnosis and detection of early stage of the disease.

Matched MeSH terms: Breast Neoplasms/immunology*
Immunohistochemical analysis of p53 expression in primary breast carcinomas

Naidu R, Yadav M, Nair S, Kutty KK

Anticancer Res, 1998 Jan-Feb;18(1A):65-70.
PMID: 9568057

Expression of p53 protein was investigated by immunohistochemical techniques in archival cases of 134 primary breast carcinomas comprising 13 comedo ductal carcinoma in situ (DCIS), 105 invasive ductal carcinomas, 7 contained the comedo DCIS component adjacent to the invasive ductal component, 5 invasive lobular carcinomas, three colloid carcinomas and one medullary carcinoma. Overexpression of p53 gene product was studied to determine the association with clinico-pathological parameters and also its relationship to c-erbB2. Overexpression of p53 protein was observed in 31% (4/13) of comedo DCIS, 37% (39/105) of invasive ductal carcinomas, 57% (4/7) of carcinomas containing both the in situ and invasive lesions and all medullary carcinomas. A significant relationship (p < 0.05) was observed between strong immunoreactivity of p53 protein and absence of estrogen receptor, histological grade and c-erbB2 but not with lymph node metastases or age of patient. These observations suggest that overexpression of p53 protein may play an important role in tumor progression from noninvasive to invasive in some breast carcinomas and may have potential as an indicator for poorer prognosis.

Matched MeSH terms: Breast Neoplasms/immunology
Fulltext Regression of solid breast tumours in mice by Newcastle disease virus is associated with production of apoptosis related-cytokines

Raihan J, Ahmad U, Yong YK, Eshak Z, Othman F, Ideris A

BMC Cancer, 2019 Apr 04;19(1):315.
PMID: 30947706 DOI: 10.1186/s12885-019-5516-5

BACKGROUND: Different strains of Newcastle disease virus (NDV) worldwide proved to have tumouricidal activity in several types of cancer cells. However, the possible anti-cancer activity of Malaysian NDV AF2240 strain and its mechanism of action remains unknown. The ability of cytokine-related apoptosis-inducing NDV AF2240 to treat breast cancer was investigated in the current study.
METHODS: A total of 90 mice were used and divided into 15 groups, each group comprising of 6 mice. Tumour, body weight and mortality of the mice were determined throughout the experiment, to observe the effect of NDV and NDV + tamoxifen treatments on the mice. In addition, the toxic effect of the treatments was determined through liver function test. In order to elucidate the involvement of cytokine production induced by NDV, a total of six cytokines, i.e. IL-6, IFN-γ, MCP-1, IL-10, IL12p70 and TNF-α were measured using cytometric bead array assay (plasma) and enzyme-linked immunosorbent spot (isolated splenocytes).
RESULTS: The results demonstrated that 4 T1 breast cancer cells in allotransplanted mice treated with AF2240 showed a noticeable inhibition of tumour growth and induce apoptotic-related cytokines.
CONCLUSIONS: NDV AF2240 suppression of breast tumour growth is associated with induction of apoptotic-related cytokines. It would be important to further investigate the molecular mechanism underlaying cytokines production by Newcastle disease virus.

Matched MeSH terms: Breast Neoplasms/immunology
Phenotyping of lymphocytes expressing regulatory and effector markers in infiltrating ductal carcinoma of the breast

Leong PP, Mohammad R, Ibrahim N, Ithnin H, Abdullah M, Davis WC, et al.

Immunol Lett, 2006 Feb 15;102(2):229-36.
PMID: 16246429

Dysfunction of the host immune system in cancer patients can be due to a number of reasons including suppression of tumour associated antigen reactive lymphocytes by regulatory T (Treg) cells. In this study, we used flow cytometry to determine the phenotype and relative abundance of the tumour infiltrating lymphocytes (TILs) from 47 enzymatically dissociated tumour specimens from patients with infiltrating ductal carcinoma (IDC) of the breast. The expression of both effector and regulatory markers on the TILs were determined by using a panel of monoclonal antibodies. Analysis revealed CD8(+) T cells (23.4+/-2.1%) were predominant in TILs, followed by CD4(+) T cells (12.6+/-1.7%) and CD56(+) natural killer cells (6.4+/-0.7%). The CD4(+)/CD8(+) ratio was 0.8+/-0.9%. Of the CD8(+) cells, there was a higher number (68.4+/-3.5%) that expressed the effector phenotype, namely, CD8(+)CD28(+) and about 46% of this subset expressed the activation marker, CD25. Thus, a lower number of infiltrating CD8(+) T cells (31.6+/-2.8%) expressed the marker for the suppressor phenotype, CD8(+)CD28(-). Of the CD4(+) T cells, 59.6+/-3.9% expressed the marker for the regulatory phenotype, CD4(+)CD25(+). About 43.6+/-3.8% CD4(+)CD25(+) subset co-expressed both the CD152 and FOXP3, the Treg-associated molecules. A positive correlation was found between the presence of CD4(+)CD25(+) subset and age (> or =50 years old) (r=0.51; p=0.045). However, no significant correlation between tumour stage and CD4(+)CD25(+) T cells was found. In addition, we also found that the CD4(+)CD25(-) subset correlated with the expression of the nuclear oestrogen receptor (ER)-alpha in the tumour cells (r=0.45; p=0.040). In conclusion, we detected the presence of cells expressing the markers for Tregs (CD4(+)CD25(+)) and suppressor (CD8(+)CD28(-)) in the tumour microenvironment. This is the first report of the relative abundance of Treg co-expressing CD152 and FOXP3 in breast carcinoma.

Matched MeSH terms: Breast Neoplasms/immunology*
Anti-idiotype vaccine against cancer

Bhattacharya-Chatterjee M, Chatterjee SK, Foon KA

Immunol Lett, 2000 Sep 15;74(1):51-8.
PMID: 10996628

Immunization with anti-idiotype (Id) antibodies represents a novel new approach to active immunotherapy. Extensive studies in animal tumor models have demonstrated the efficacy of anti-Id vaccines in preventing tumor growth and curing mice with established tumor. We have developed and characterized several murine monoclonal anti-Id antibodies (Ab2) which mimic distinct human tumor-associated antigens (TAA) and can be used as surrogate antigens for triggering active anti-tumor immunity in cancer patients. Encouraging results have been obtained in recent clinical trials. In this article, we will review the existing literature and summarize our own findings showing the potential of this approach for various human cancers. We will also discuss where anti-Id vaccines may perform better than traditional antigen vaccines.

Matched MeSH terms: Breast Neoplasms/immunology
Fulltext The molecular landscape of Asian breast cancers reveals clinically relevant population-specific differences

Pan JW, Zabidi MMA, Ng PS, Meng MY, Hasan SN, Sandey B, et al.

Nat Commun, 2020 Dec 22;11(1):6433.
PMID: 33353943 DOI: 10.1038/s41467-020-20173-5

Molecular profiling of breast cancer has enabled the development of more robust molecular prognostic signatures and therapeutic options for breast cancer patients. However, non-Caucasian populations remain understudied. Here, we present the mutational, transcriptional, and copy number profiles of 560 Malaysian breast tumours and a comparative analysis of breast cancers arising in Asian and Caucasian women. Compared to breast tumours in Caucasian women, we show an increased prevalence of HER2-enriched molecular subtypes and higher prevalence of TP53 somatic mutations in ER+ Asian breast tumours. We also observe elevated immune scores in Asian breast tumours, suggesting potential clinical response to immune checkpoint inhibitors. Whilst HER2-subtype and enriched immune score are associated with improved survival, presence of TP53 somatic mutations is associated with poorer survival in ER+ tumours. Taken together, these population differences unveil opportunities to improve the understanding of this disease and lay the foundation for precision medicine in different populations.

Matched MeSH terms: Breast Neoplasms/immunology

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