Immune Checkpoint Inhibitors in Triple Negative Breast Cancer Treatment: Promising Future Prospects.

Published on Feb 25, 2021in Frontiers in Oncology6.244
· DOI :10.3389/FONC.2020.600573
Remy Thomas6
Estimated H-index: 6
(Khalifa University),
Ghaneya Al-Khadairi4
Estimated H-index: 4
(Khalifa University),
Julie Decock20
Estimated H-index: 20
(Khalifa University)
Immunotherapy has emerged as the fifth pillar of cancer treatment alongside surgery, radiotherapy, chemotherapy and targeted therapy. Immune checkpoint inhibitors are the current superheroes of immunotherapy, unleashing a patient’s own immune cells to kill tumors and revolutionizing cancer treatment in a variety of cancers. Although breast cancer was historically believed to be immunologically silent, treatment with immune checkpoint inhibitors has been shown to induce modest responses in metastatic breast cancer. Given the inherent heterogeneity of breast tumors, this raised the question whether certain breast tumors might benefit more from immune-based interventions and which cancer cell-intrinsic and/or microenvironmental factors define the likelihood of inducing a potent and durable anti-tumor immune response. In this review, we will focus on triple negative breast cancer as immunogenic breast cancer subtype, and specifically discuss the relevance of tumor mutational burden, the plethora and diversity of tumor infiltrating immune cells in addition to the immunoscore, the presence of immune checkpoint expression, and the microbiome in defining immune checkpoint blockade response. We will highlight the current immune checkpoint inhibitor treatment options, either as monotherapy or in combination with standard-of-care treatment modalities such as chemotherapy and targeted therapy. In addition, we will look into the potential of immunotherapy-based combination strategies using immune checkpoint inhibitors to enhance both innate and adaptive immune responses, or to establish a more immune favorable environment for cancer vaccines. Finally, the review will address the need for unambiguous predictive biomarkers as one of the main challenges of immune checkpoint blockade. To conclude, the potential of immune checkpoint blockade for triple negative breast cancer treatment could be enhanced by exploration of aforementioned factors and treatment strategies thereby providing promising future prospects.
#1Javier CortesH-Index: 79
#2David W. Cescon (Princess Margaret Cancer Centre)H-Index: 31
Last. Valdes-Albini FrancesH-Index: 1
view all 227 authors...
Background Pembrolizumab monotherapy showed durable antitumour activity and manageable safety in patients with metastatic triple-negative breast cancer. We aimed to examine whether the addition of pembrolizumab would enhance the antitumour activity of chemotherapy in patients with metastatic triple-negative breast cancer. Methods In this randomised, placebo-controlled, double-blind, phase 3 trial, done in 209 sites in 29 countries, we randomly assigned patients 2:1 with untreated locally recurre...
#1Elizabeth A. Mittendorf (Brigham and Women's Hospital)H-Index: 71
#2H. Zhang (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 1
Last. Nadia Harbeck (LMU: Ludwig Maximilian University of Munich)H-Index: 88
view all 20 authors...
Summary Background Preferred neoadjuvant regimens for early-stage triple-negative breast cancer (TNBC) include anthracycline-cyclophosphamide and taxane-based chemotherapy. IMpassion031 compared efficacy and safety of atezolizumab versus placebo combined with nab-paclitaxel followed by doxorubicin plus cyclophosphamide as neoadjuvant treatment for early-stage TNBC. Methods This double-blind, randomised, phase 3 study enrolled patients in 75 academic and community sites in 13 countries. Patients ...
#1Isaac S. Chan (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 4
#2Hildur Knutsdottir (Johns Hopkins University)H-Index: 7
Last. Andrew J. Ewald (Johns Hopkins University)H-Index: 42
view all 11 authors...
Natural killer (NK) cells have potent antitumor and antimetastatic activity. It is incompletely understood how cancer cells escape NK cell surveillance. Using ex vivo and in vivo models of metastasis, we establish that keratin-14+ breast cancer cells are vulnerable to NK cells. We then discovered that exposure to cancer cells causes NK cells to lose their cytotoxic ability and promote metastatic outgrowth. Gene expression comparisons revealed that healthy NK cells have an active NK cell molecula...
#1Yu-Yang Jiang (UGA: University of Georgia)H-Index: 7
#2Wolfgang Maier (University of Freiburg)H-Index: 24
Last. Jacek Gaertig (UGA: University of Georgia)H-Index: 37
view all 11 authors...
Not much is known about how organelles organize into patterns. In ciliates, the cortical pattern is propagated during "tandem duplication," a cell division that remodels the parental cell into two daughter cells. A key step is the formation of the division boundary along the cell's equator. In Tetrahymena thermophila, the cdaA alleles prevent the formation of the division boundary. We find that the CDAA gene encodes a cyclin E that accumulates in the posterior cell half, concurrently with accumu...
#1Franck PagèsH-Index: 34
#2Thierry André (University of Paris)H-Index: 82
Last. Jean-François Emile (French Institute of Health and Medical Research)H-Index: 81
view all 21 authors...
Abstract Background The Immunoscore (IS), which prognostically classifies stage I-III colon cancer (CC) patients, was evaluated in the IDEA France cohort study investigating 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy in stage III CC patients. Patients and Methods Densities of CD3+ and CD8+ T-cells in the tumor and invasive margin were determined by immunohistochemistry, quantified by digital pathology, and converted to IS. Mismatch repair status was determined by immunohistoche...
#1Jennifer L. McQuade (University of Texas MD Anderson Cancer Center)H-Index: 26
#2Gabriel Ologun (University of Texas MD Anderson Cancer Center)H-Index: 4
Last. Jennifer A. Wargo (University of Texas MD Anderson Cancer Center)H-Index: 90
view all 4 authors...
PURPOSE OF REVIEW We review emerging evidence regarding the impact of gut microbes on antitumor immunity, and ongoing efforts to translate this in clinical trials. RECENT FINDINGS Pre-clinical models and human cohort studies support a role for gut microbes in modulating overall immunity and immunotherapy response, and numerous trials are now underway exploring strategies to modulate gut microbes to enhance responses to cancer therapy. This includes the use of fecal microbiota transplant (FMT), w...
#1Frank A. Sinicrope (Mayo Clinic)H-Index: 68
#2Qian Shi (UR: University of Rochester)H-Index: 32
Last. Steven R. Alberts (Mayo Clinic)H-Index: 77
view all 14 authors...
Background The American Joint Committee on Cancer staging and other prognostic tools fail to account for stage-independent variability in outcome. We developed a prognostic classifier adding Immunoscore to clinicopathological and molecular features in patients with stage III colon cancer. Methods Patient (n = 559) data from the FOLFOX arm of adjuvant trial NCCTG N0147 were used to construct Cox models for predicting disease-free survival (DFS). Variables included age, sex, T stage, positive lymp...
#1Deborah Nejman (Weizmann Institute of Science)H-Index: 10
#2Ilana Livyatan (Weizmann Institute of Science)H-Index: 2
Last. Ravid Straussman (Weizmann Institute of Science)H-Index: 21
view all 61 authors...
Bacteria were first detected in human tumors more than 100 years ago, but the characterization of the tumor microbiome has remained challenging because of its low biomass. We undertook a comprehensive analysis of the tumor microbiome, studying 1526 tumors and their adjacent normal tissues across seven cancer types, including breast, lung, ovary, pancreas, melanoma, bone, and brain tumors. We found that each tumor type has a distinct microbiome composition and that breast cancer has a particularl...
#1Javier CortesH-Index: 79
#2David W. Cescon (Princess Margaret Cancer Centre)H-Index: 31
Last. Esther HolgadoH-Index: 17
view all 20 authors...
1000Background: Pembrolizumab (pembro) monotherapy showed promising antitumor activity and manageable safety in patients (pts) with metastatic TNBC in KEYNOTE-012, -086 and -119. KEYNOTE-355 (Clini...
#1Zuzana KosH-Index: 12
#2Elvire Roblin (Université Paris-Saclay)H-Index: 2
Last. Sandra Demaria (Cornell University)H-Index: 69
view all 93 authors...
Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and...
Cited By6
#1Marina Petrenko (MLU: Martin Luther University of Halle-Wittenberg)H-Index: 3
#2Antje Güttler (MLU: Martin Luther University of Halle-Wittenberg)H-Index: 11
Last. René Csuk (MLU: Martin Luther University of Halle-Wittenberg)H-Index: 28
view all 12 authors...
Abstract null null Many pentacyclic triterpenoids show anti-cancer and anti-inflammatory properties. Recently, we detected a pronounced cytotoxicity and radiosensitivity of two betulinyl sulfamates in human breast cancer cells. Besides betulinic acid scaffold (BSBA-S), we synthesized several new sulfamate-coupled scaffolds from oleanolic acid (OSBA-S), ursolic acid (USBA-S), platanic acid (PSBA-S) and maslinic acid (MSBA-S). Highest cytotoxicity was monitored in breast cancer cell lines after MS...
#1Fokhrul Hossain (LSU Health Sciences Center New Orleans)H-Index: 11
#2Samarpan Majumder (LSU Health Sciences Center New Orleans)H-Index: 2
Last. Lucio Miele (LSU Health Sciences Center New Orleans)H-Index: 65
view all 5 authors...
Triple-negative breast cancer (TNBC) is an aggressive, molecularly heterogeneous subtype of breast cancer. Obesity is associated with increased incidence and worse prognosis in TNBC through various potential mechanisms. Recent evidence suggests that the gut microbiome plays a central role in the progression of cancer, and that imbalances or dysbiosis in the population of commensal microbiota can lead to inflammation and contribute to tumor progression. Obesity is characterized by low-grade infla...
#1Adviti Naik (Khalifa University)H-Index: 8
#2Remy Thomas (Khalifa University)H-Index: 6
Last. Julie Decock (Khalifa University)H-Index: 20
view all 6 authors...
PReferentially expressed Antigen in Melanoma (PRAME) is a cancer testis antigen with restricted expression in somatic tissues and re-expression in poor prognostic solid tumours. PRAME has been extensively investigated as a target for immunotherapy, however, its role in modulating the anti-tumour immune response remains largely unknown. Here, we show that PRAME tumour expression is associated with worse survival in the TCGA breast cancer cohort, particularly in immune-unfavourable tumours. Using ...
#1Elizabeth Rapp Berger (Yale University)H-Index: 2
#2Tristen S. Park (Yale University)H-Index: 10
Last. Nita Ahuja (Yale University)H-Index: 64
view all 6 authors...
Triple-negative breast cancer (TNBC) is considered one of the highest-risk subtypes of breast cancer and has dismal prognosis. Local recurrence rate after standard therapy in the early breast cancer setting can be upwards to 72% in 5 years, and in the metastatic setting, the 5-year overall survival is 12%. Due to the lack of receptor expression, there has been a paucity of targeted therapeutics available, with chemotherapy being the primary option for systemic treatment in both the neoadjuvant a...
#1Xiao-Li Yang (Tongji University)H-Index: 4
#2Yi Shi (Tongji University)H-Index: 4
Last. Da Fu (Tongji University)H-Index: 18
view all 12 authors...
Abstract Cancer accounted for 16% of all death worldwide in 2018. Significant progress has been made in understanding tumor occurrence, progression, diagnosis, treatment, and prognosis at the molecular level. However, genomics changes cannot truly reflect the state of protein activity in the body due to the poor correlation between genes and proteins. Quantitative proteomics, capable of quantifying the relatively different protein abundance in cancer patients, has been increasingly adopted in ca...
#1Anindita Chakrabarty (Shiv Nadar University)H-Index: 18
#2Shayantani Chakraborty (Shiv Nadar University)
Last. Goutam ChowdhuryH-Index: 24
view all 4 authors...
Triple negative breast cancer (TNBC) is classically treated with combination chemotherapies. Although, initially responsive to chemotherapies, TNBC patients frequently develop drug-resistant, metastatic disease. Chemotherapy resistance can develop through many mechanisms, including induction of a transient growth-arrested state, known as the therapy-induced senescence (TIS). In this paper, we will focus on chemoresistance in TNBC due to TIS. One of the key characteristics of senescent cells is a...
BACKGROUND The prognosis of early breast cancer is linked to clinic-pathological stage and the molecular characteristics of intrinsic tumor cells. In some patients, the amount and quality of tumor-infiltrating immune cells appear to affect long term outcome. We aimed to propose a new tool to estimate immune infiltrate, and link these factors to patient prognosis according to breast cancer molecular subtypes. METHODS We performed in silico analyses in more than 2800 early breast cancer transcript...
This website uses cookies.
We use cookies to improve your online experience. By continuing to use our website we assume you agree to the placement of these cookies.
To learn more, you can find in our Privacy Policy.