Pembrolizumab for Early Triple-Negative Breast Cancer

Schmid, Peter; Cortés, Javier; Pusztai, Lajos; McArthur, Heather L.; Kümmel, Sherko; Bergh, Jonas; Denkert, Carsten; Park, Yeon Hee; Hui, Rina; Harbeck, Nadia; Takahashi, Masato; Foukakis, Theodoros; Fasching, Peter A.; Cardoso, Fátima; Untch, Michael; Jia, Liyi; Karantza, Vassiliki; Zhao, Jing; Aktan, Gursel; Dent, Rebecca; O’Shaughnessy, Joyce; Investigators, Keynote

doi:10.1056/nejmoa1910549

Cited by 2,022 publications

(1,741 citation statements)

References 30 publications

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“…227 Results from the KEYNOTE-522 phase 3 trial examining neoadjuvant pembrolizumab with chemotherapy or chemotherapy alone, followed by adjuvant pembrolizumab or placebo in TNBC patients with early disease were recently published in New England Journal of Medicine. 228 PD-L1-positive metastatic TNBC in the IMpassion130, 223 Schmid's study using neoadjuvant plus adjuvant pembrolizumab was effective regardless of PD-L1 expression levels. 228 Targeting solid tumors with ICB is difficult but the field continues to push forward to find novel ways to improve anti-tumor immunity.…”

Section: Anti -Tumor Immunit Ymentioning

confidence: 99%

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Microbiome, bile acids, and obesity: How microbially modified metabolites shape anti‐tumor immunity

Sipe

Chaib

Pingili

et al. 2020

Immunological Reviews

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Bile acids (BAs) are known facilitators of nutrient absorption but recent paradigm shifts now recognize BAs as signaling molecules regulating both innate and adaptive immunity. Bile acids are synthesized from cholesterol in the liver with subsequent microbial modification and fermentation adding complexity to pool composition. Bile acids act on several receptors such as Farnesoid X Receptor and the G proteincoupled BA receptor 1 (TGR5). Interestingly, BA receptors (BARs) are expressed on immune cells and activation either by BAs or BAR agonists modulates innate and adaptive immune cell populations skewing their polarization toward a more tolerogenic anti-inflammatory phenotype. Intriguingly, recent evidence also suggests that BAs promote anti-tumor immune response through activation and recruitment of tumoricidal immune cells such as natural killer T cells. These exciting findings have redefined BA signaling in health and disease wherein they may suppress inflammation on the one hand, yet promote anti-tumor immunity on the other hand. In this review, we provide our readers with the most recent understanding of the interaction of BAs with the host microbiome, their effect on innate and adaptive immunity in health and disease with a special focus on obesity, bariatric surgery-induced weight loss, and immune checkpoint blockade in cancer. K E Y W O R D S bariatric surgery, immunometabolism, microbiome, mitochondria, obesity, tumor microenvironment | 221 SIPE Et al.

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Section: Anti -Tumor Immunit Ymentioning

confidence: 99%

“…228 PD-L1-positive metastatic TNBC in the IMpassion130, 223 Schmid's study using neoadjuvant plus adjuvant pembrolizumab was effective regardless of PD-L1 expression levels. 228 Targeting solid tumors with ICB is difficult but the field continues to push forward to find novel ways to improve anti-tumor immunity.…”

Section: Anti -Tumor Immunit Ymentioning

confidence: 99%

Microbiome, bile acids, and obesity: How microbially modified metabolites shape anti‐tumor immunity

Sipe

Chaib

Pingili

et al. 2020

Immunological Reviews

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“…To further elucidate the inherent correlations between immunologic phenotypes and distinct prognostic outcomes, the curated gene list of immune modulators was adopted [15], of which the correlogram was suggestive of evident collections consisted of these immune-related components. With the in-depth illustration of immunoediting theory and evolution of immunotherapy, immune checkpoints have been considered with cruciality in cancer immunity response, and the developed inhibitors have been dramatically improving the prognosis of several types of malignancies [21][22][23]. Herein, immune checkpoints were selected to be evaluated between these two pIRS groups.…”

Section: Discussionmentioning

confidence: 99%

Tumor microenvironment subtypes and immune-related signatures for the prognosis of breast cancer

Wang

Xu²

2020

Preprint

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To better understand the heterogeneity of tumor microenvironment (TME) and establish a prognostic model for breast cancer in clinical practice, the leukocyte infiltrations of 22 cell types of interest from 2620 breast cancer patients were quantitatively estimated using deconvolution algorithms, and three TME subtypes with distinct molecular and clinical features were identified by unsupervised clustering approach. Then, we carried out systematic analyses to illustrate the contributing mechanisms for differential phenotypes, which suggested that the divergences were distinguished by cell cycle dysfunction, variation of cytotoxic T lymphocytes activity. Next, through dimensionally reduction and selection based on random-forest analysis, least absolute shrinkage and selection operator (LASSO) analysis, and uni- and multivariate COX regression analysis, a total of 15 significant genes were proposed to construct the prognostic immune-related score (pIRS) system and, in combinations with clinicopathological characteristics, a predictive model was ultimately built with well performance for survival of breast cancer patients. Comparative analyses demonstrated that proactivity of CD8 T lymphocytes and hyper-angiogenesis could be attributed to distinct prognostic outcomes. In conclusion, we retrieved three TME phenotypes and the curated prognostic model based on pIRS system for breast cancer. This model is justified for validation and optimized in the coming future.

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“…In the context of immunotherapy approaches in breast cancer, it should also be acknowledged that results on early TNBCs treated in neoadjuvant studies with combination of chemotherapy and immunotherapy are now available. The phase III KEYNOTE-522 trial has recently shown significantly higher pCR rates for those patients treated with the addition of pembrolizumab to chemotherapy [123]. Although a higher pCR rate was observed for the PD-L1-positive tumors, the difference was not statistically significant.…”

Section: Immunotherapy In Breast Cancermentioning

confidence: 95%

The Multifaceted Nature of Tumor Microenvironment in Breast Carcinomas

et al. 2020

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Heterogeneity in breast carcinomas can be appreciated at various levels, from morphology to molecular alterations, and there are well-known genotypic-phenotypic correlations. Clinical decision-making is strictly focused on the evaluation of tumor cells and is based on the assessment of hormone receptors and of the HER2 status, by means of a combination of immunohistochemical and in situ hybridization techniques. The tumor microenvironment (TME) also shows a multifaceted nature stemming from the different actors populating the intratumoral and the peritumoral stroma of breast carcinomas. Of note, we have now evidence that tumor-infiltrating lymphocytes (TILs) are clinically meaningful as their quantification in the intratumoral stroma strongly correlates with good prognosis, in particular in triple-negative and HER2-positive breast cancer patients. Nevertheless, TILs are just one of the many actors orchestrating the com-plexity of the TME, which is populated by immune and nonimmune cells (cancer-associated fibroblasts, cancer-associated adipocytes), as well as non-cellular components such as chemical inflammation mediators. In this review article we will overview the main features of the distinct cell compartments by discussing (i) the potential impact the TME may have on the prognostic stratification of breast cancers and (ii) the possible predictive value of some markers in the context of immunotherapy in light of the recent results of phase III studies in advanced and early triple-negative breast cancer patients.

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Pembrolizumab for Early Triple-Negative Breast Cancer

Cited by 2,022 publications

References 30 publications

Microbiome, bile acids, and obesity: How microbially modified metabolites shape anti‐tumor immunity

Microbiome, bile acids, and obesity: How microbially modified metabolites shape anti‐tumor immunity

Tumor microenvironment subtypes and immune-related signatures for the prognosis of breast cancer

The Multifaceted Nature of Tumor Microenvironment in Breast Carcinomas

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