scholarly journals The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Khalid El Bairi ◽  
Harry R. Haynes ◽  
Elizabeth Blackley ◽  
Susan Fineberg ◽  
Jeffrey Shear ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Working Group ◽  
Checkpoint Inhibitors ◽  
Tumor Infiltrating Lymphocytes ◽  
Current Status ◽  
Middle Income ◽  
Patient Advocate ◽  
Clinical Utilization ◽  
Programmed Death ◽  
Signaling Axis

AbstractThe advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.

scholarly journals Current status of PD-1/PD-L1 blockade immunotherapy in breast cancer

2020 ◽  
Author(s):  
Emi Noguchi ◽  
Tadahiko Shien ◽  
Hiroji Iwata
Keyword(s):  
Breast Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Tumor Infiltrating Lymphocytes ◽  
The United States ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Current Status ◽  
Infiltrating Lymphocytes

Abstract Over the past 10 years, immunotherapy with immune checkpoint inhibitors has revolutionized the management of various cancers. However, immunotherapy in breast cancer has not been successful. Breast cancer has long been recognized as an immunologically ‘cold’ tumor, although a higher frequency of tumor-infiltrating lymphocytes present in certain subtypes and an association between tumor-infiltrating lymphocytes and favorable prognosis have been reported. In March 2019, the combination of atezolizumab and nanoparticle albumin-bound paclitaxel was granted accelerated approval in the United States for the treatment of programmed death-ligand 1-positive advanced or metastatic triple-negative breast cancer. This finally opened the door for immune checkpoint blockade therapy for breast cancer. Several clinical trials have been conducted using different combinations of immune checkpoint inhibitors and chemotherapy or targeted agents in various treatment settings for metastatic breast cancer and early-stage breast cancer. In this review, we summarize recent advances in immune checkpoint blockade therapy and predictive biomarkers in breast cancer.

scholarly journals Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 636 ◽  
Author(s):  
Regina Padmanabhan ◽  
Hadeel Shafeeq Kheraldine ◽  
Nader Meskin ◽  
Semir Vranic ◽  
Ala-Eddin Al Moustafa
Keyword(s):  
Breast Cancer ◽  
Mathematical Models ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Breast Cancers ◽  
Treatment Protocols ◽  
Cancer Subtypes ◽  
Cancer Management ◽  
Her2 Breast Cancer ◽  
Programmed Death

Breast cancer is one of the major causes of mortality in women worldwide. The most aggressive breast cancer subtypes are human epidermal growth factor receptor-positive (HER2+) and triple-negative breast cancers. Therapies targeting HER2 receptors have significantly improved HER2+ breast cancer patient outcomes. However, several recent studies have pointed out the deficiency of existing treatment protocols in combatting disease relapse and improving response rates to treatment. Overriding the inherent actions of the immune system to detect and annihilate cancer via the immune checkpoint pathways is one of the important hallmarks of cancer. Thus, restoration of these pathways by various means of immunomodulation has shown beneficial effects in the management of various types of cancers, including breast. We herein review the recent progress in the management of HER2+ breast cancer via HER2-targeted therapies, and its association with the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) axis. In order to link research in the areas of medicine and mathematics and point out specific opportunities for providing efficient theoretical analysis related to HER2+ breast cancer management, we also review mathematical models pertaining to the dynamics of HER2+ breast cancer and immune checkpoint inhibitors.

scholarly journals Checkpoint Inhibitors in Breast Cancer - Current Status and Future Directions

Breast Care ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. 27-31 ◽  
Author(s):  
Joachim Bischoff
Keyword(s):  
Breast Cancer ◽  
T Cell Activation ◽  
Cell Activation ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Death Receptor ◽  
Target Population ◽  
Current Status ◽  
Immune Checkpoints ◽  
Breast Cancer Patients

Antineoplastic agents directly targeting tumor cells have represented the major strategy of systemic anticancer therapy for many years. Nevertheless, overcoming resistance mechanisms remains a great challenge because treatment options are limited in many cases. From this point of view, immunotherapeutic approaches seem promising in a broad spectrum of solid tumors. These include in particular the currently available inhibitors directed against immune checkpoints leading to a significant T-cell activation. To date, the programmed death receptor 1 (PD-1) and its ligand are the most prominent targets in this context. However, the role of checkpoint inhibitors in the treatment of breast cancer is still being debated, and the main focus is on triple-negative breast cancer patients as a target population in many ongoing trials. Moreover, the potential superiority of combinations with other anticancer drugs such as cytotoxics and targeted agents will be discussed.

scholarly journals Blockade of PD-1, PD-L1, and TIM-3 Altered Distinct Immune- and Cancer-Related Signaling Pathways in the Transcriptome of Human Breast Cancer Explants

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 703
Author(s):  
Reem Saleh ◽  
Salman M. Toor ◽  
Dana Al-Ali ◽  
Varun Sasidharan Nair ◽  
Eyad Elkord
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Checkpoint Inhibitors ◽  
Rna Seq ◽  
Human Breast ◽  
Compensatory Mechanisms ◽  
Transcriptomic Data ◽  
Functional Studies ◽  
Programmed Death ◽  
Cell Death Protein

Immune checkpoint inhibitors (ICIs) are yet to have a major advantage over conventional therapies, as only a fraction of patients benefit from the currently approved ICIs and their response rates remain low. We investigated the effects of different ICIs—anti-programmed cell death protein 1 (PD-1), anti-programmed death ligand-1 (PD-L1), and anti-T cell immunoglobulin and mucin-domain containing-3 (TIM-3)—on human primary breast cancer explant cultures using RNA-Seq. Transcriptomic data revealed that PD-1, PD-L1, and TIM-3 blockade follow unique mechanisms by upregulating or downregulating distinct pathways, but they collectively enhance immune responses and suppress cancer-related pathways to exert anti-tumorigenic effects. We also found that these ICIs upregulated the expression of other IC genes, suggesting that blocking one IC can upregulate alternative ICs, potentially giving rise to compensatory mechanisms by which tumor cells evade anti-tumor immunity. Overall, the transcriptomic data revealed some unique mechanisms of the action of monoclonal antibodies (mAbs) targeting PD-1, PD-L1, and TIM-3 in human breast cancer explants. However, further investigations and functional studies are warranted to validate these findings.

Translational Breast Cancer Research Consortium (TBCRC) Patient Advocate Working Group (PAWG): An approach to research advocacy.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. e19539-e19539
Author(s):  
C. Chauhan ◽  
M. L. Smith ◽  
N. E. Carbine ◽  
L. Cargen ◽  
D. K. Cline ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Research ◽  
Working Group ◽  
Breast Cancer Research ◽  
Patient Advocate ◽  
Research Consortium

scholarly journals Current Status and Future Projections of Breast Cancer in Asia

Breast Care ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. 372-378 ◽  
Author(s):  
Lei Fan ◽  
Paul E. Goss ◽  
Kathrin Strasser-Weippl
Keyword(s):  
Breast Cancer ◽  
Socioeconomic Development ◽  
Control Measures ◽  
Current Status ◽  
Breast Cancers ◽  
Asian Countries ◽  
Middle Income ◽  
Cancer Risk Factors ◽  
Western Countries ◽  
Breast Cancer Risk Factors

Asia is the world's largest continent comprising about 3/5 of the human population. Breast cancer is the most common type of cancer and the second leading cause of cancer-related deaths among women in Asia, accounting for 39% of all breast cancers diagnosed worldwide. The incidence of breast cancer in Asia varies widely across the continent and is still lower than in Western countries, but the proportional contribution of Asia to the global breast cancer rates is increasing rapidly in parallel to the socioeconomic development. However, the mortality-to-incidence ratios are much higher for Asia than for Western countries. Most Asian countries are low- and middle-income countries (LMICs) where breast cancer presents at a younger age and a later stage, and where patients are more likely to die from the disease than those in Western countries. Moreover, diagnostic workup, treatment and palliative services are inadequate in most Asian LMICs. In this review, we present an overview of the breast cancer risk factors and epidemiology, control measures, and cancer care among Asian countries.

scholarly journals Immunotherapy for Patients with Advanced Urothelial Cancer: Current Evidence and Future Perspectives

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Clizia Zichi ◽  
Marcello Tucci ◽  
Gianmarco Leone ◽  
Consuelo Buttigliero ◽  
Francesca Vignani ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Adaptive Immune Response ◽  
Tumor Infiltrating Lymphocytes ◽  
Invasive Disease ◽  
Current Evidence ◽  
Programmed Death

In recent years, immunotherapy has produced encouraging results in a rapidly increasing number of solid tumors. The responsiveness of bladder cancer to immunotherapy was first established in nonmuscle invasive disease in 1976 with intravesical instillations of bacillus Calmette-Guérin (BCG). Very recently immune checkpoint inhibitors demonstrated good activity and significant efficacy in metastatic disease. In particular the best results were obtained with programmed death-ligand-1 (PD-L1) and programmed death-1 (PD-1) inhibitors, but many other immune checkpoint inhibitors, including anti-cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) antibodies, are currently under investigation in several trials. Simultaneously other therapeutic strategies which recruit an adaptive immune response against tumoral antigens or employ externally manipulated tumor infiltrating lymphocytes might change the natural history of bladder cancer in the near future. This review describes the rationale for the use of immunotherapy in bladder cancer and discusses recent and ongoing clinical trials with checkpoint inhibitors and other novel immunotherapy agents.

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