Leukocytes in Mammary Development and Cancer

Coussens, Lisa M.; Pollard, Jeffrey W.

doi:10.1101/cshperspect.a003285

Cited by 171 publications

(141 citation statements)

References 142 publications

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“…On the other hand, tumors create an immunosuppressive microenvironment, involving M2 or anti-inflammatory macrophages and regulatory T cells versus cytotoxic T cells [44][45][46]. M2 macrophages express different signaling molecules and cell surface receptors than their M1 counterpart, most notably signaling molecules of the TGFb pathway, IL10 and STAT3 signaling and molecules such as VEGF, promoting angiogenesis [47].…”

Section: Discussionmentioning

confidence: 99%

Leveraging Naked Mole Rat (Heterocephalus glaber) Comparative Genomics to Identify Canine Genes Modulating Susceptibility to Tumorigenesis and Cancer Phenotypes

Irizarry¹,

Punt²

2015

J Veterinar Sci Technol

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We utilized a comparative genomics approach to analyze a core set of tumorigenesis orthologs among human, mouse, dog and naked mole rat. The analysis identified cancer orthologs that are both conserved and divergent between dog and the cancer resistant species naked mole rat. These tumorigenesis orthologous are associated with phenotypes that modulate cancer susceptibility, cardiac development, craniofacial development, brain development, skeletal development, and immune function, to name a few. This bioinformatics approach employed a variety of literature mining tools to further uncover relationships between the tumorigenesis orthologs. Together, these results shed light on the relationship between breed formations, breed associated morphological traits and breed associated susceptibility to tumorigenesis. These findings support the use of a comparative genomic analysis between species with dramatically different disease phenotypes as a gene discovery tool. A total of 146 proteins coding SNPs were identified in these tumorigenesis orthologs representing missense variations, frame shift variations and nonsense variations. The genes identified in this study can serve as a list of candidates for subsequent laboratory and clinical study. Furthermore, the identification of SNPs impacting the primary structure of the tumorigenesis orthologs may provide clues about the basis of cancer susceptibility between dog breeds.

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Section: Discussionmentioning

confidence: 99%

Leveraging Naked Mole Rat (Heterocephalus glaber) Comparative Genomics to Identify Canine Genes Modulating Susceptibility to Tumorigenesis and Cancer Phenotypes

Irizarry¹,

Punt²

2015

J Veterinar Sci Technol

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“…Consequently, 25 patients were considered evaluable for the main analysis (28 patients on an intent-to-treat basis). Among evaluable patients (71%), only 10 received six cycles of therapy associated six cycles of docetaxel [1][2][3][4][5][6] and 15 cetuximab infusions [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] (Fig. 1).…”

Section: Treatment Dispositionmentioning

confidence: 99%

Multicentric neoadjuvant pilot Phase II study of cetuximab combined with docetaxel in operable triple negative breast cancer

et al. 2015

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Systemic therapy for triple negative breast cancer (TNBC) is mostly based upon chemotherapy. Epithelial Growth Factor Receptor (EGFR) is overexpressed in around 50% of TNBC and may play a role in its pathogenesis. Consequently, we performed a multicentric pilot Phase II neoadjuvant trial of cetuximab (anti-EGFR antibody) combined with docetaxel for patients with operable, Stage II-III TNBC. Therapy consisted of weekly cetuximab (first infusion: 400 mg/m 2 , then 250 mg/m 2 ) combined with six cycles of docetaxel (T: 100 mg/m 2 ) q.3 weeks. Subsequently, all patients underwent surgery. The primary endpoint was pathological complete response (pCR) while clinical response, toxicity and ancillary studies were secondary endpoints. Paraffin-embedded and frozen tumor samples were systematically collected in order to identify predictive biomarkers of efficacy and resistance. From a total of 35 accrued patients, 25 were assessable for pathologic response. The pCR rate was 24% . Complete clinical response rate (cCR) was observed in 22% of cases. Conservative surgery was performed in 75% of patients. Toxicity, mostly cutaneous and hematologic, was manageable. The pre-therapy ratio between CD81 and FOXP31 tumor-infiltrating lymphocytes equal or higher than 2.75 was predictive of pCR: 43% versus 0%, p 5 0.047. Cetuximab in combination with docetaxel displays a modest activity, but acceptable toxicity as neoadjuvant therapy of operable TNBC. Similarly to previous observations using panitumumab, another anti-EGFR antibody, the immune component of the tumor microenvironment may play an important role in predicting TNBC response to the neoadjuvant therapy.Breast cancer (BC), the most frequent cancer in women, represents a heterogeneous disease in terms of clinical, histological and molecular classifications. 1 Triple negative breast cancer (TNBC) is defined by the immunohistochemical (IHC) negativity for estrogen/progesterone receptors (ER/PR) and the lack of human epidermal growth factor 2 (HER2) gene amplification. 2TNBC accounts for about 15% of BC and is known to be an aggressive entity with high rates of relapse and poor prognosis. Molecular stratification has recently revealed that majority of TNBC cases are essentially basal-like BC (71-91%) with overexpression of EGF receptor (EGFR) in around 50% of cases. 4-7Presently, therapeutic approaches for TNBC appear monolithic, largely based upon cytotoxics. Neoadjuvant chemotherapy (NACT) has recently emerged as a treatment option for patients with operable TNBC with proven correlation between pathological complete response (pCR) and survival. 8 In patients with TNBC pCR rates are reported to be around 12% with taxane monotherapy and 12 to 39% with taxane/ anthracycline combinations.

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“…Chronic inflammation in the tumor microenvironment and the resulting tumor evasion of the immune system have recently been recognized as another hallmark of cancer (Hanahan and Weinberg, 2011). Although pre-existing inflammation and infection are not considered a risk factor for breast cancer development, it is generally accepted that infiltration of immunosuppressive leukocytes and accompanying chronic inflammation during tumor progression promote breast cancer growth (DeNardo and Coussens, 2007;Coussens and Pollard, 2011;Coussens et al, 2013). This review will focus on the protumorigenic immune cell subsets and proinflammatory mediators that form suppressive tumor microenvironments and the most recent findings in human breast cancer immunotherapeutics.…”

Section: Introductionmentioning

confidence: 99%

Harnessing the immune system for the treatment of breast cancer

Jiang

2014

J. Zhejiang Univ. Sci. B

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Abstract:Standard treatment options for breast cancer include surgery, chemotherapy, radiation, and targeted therapies, such as adjuvant hormonal therapy and monoclonal antibodies. Recently, the recognition that chronic inflammation in the tumor microenvironment promotes tumor growth and survival during different stages of breast cancer development has led to the development of novel immunotherapies. Several immunotherapeutic strategies have been studied both preclinically and clinically and already have been shown to enhance the efficacy of conventional treatment modalities. Therefore, therapies targeting the immune system may represent a promising next-generation approach for the treatment of breast cancers. This review will discuss recent findings that elucidate the roles of suppressive immune cells and proinflammatory cytokines and chemokines in the tumor-promoting microenvironment, and the most current immunotherapeutic strategies in breast cancer.

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Leukocytes in Mammary Development and Cancer

Cited by 171 publications

References 142 publications

Leveraging Naked Mole Rat (Heterocephalus glaber) Comparative Genomics to Identify Canine Genes Modulating Susceptibility to Tumorigenesis and Cancer Phenotypes

Leveraging Naked Mole Rat (Heterocephalus glaber) Comparative Genomics to Identify Canine Genes Modulating Susceptibility to Tumorigenesis and Cancer Phenotypes

Multicentric neoadjuvant pilot Phase II study of cetuximab combined with docetaxel in operable triple negative breast cancer

Harnessing the immune system for the treatment of breast cancer

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