Role of Immune Response in Breast Cancer Vaccines

The immune system plays a major role in cancer surveillance. Harnessing its power to treat many cancers is now a reality that has led to cures in hopeless situations where no other solutions were available from traditional anticancer drugs. These spectacular achievements rekindled the oncology community’s interest in extending the benefits to all cancers including breast cancer. The first section of this article reviews the biological foundations of the immune response to different subtypes of breast cancer and the ways cancer may overcome the immune attack leading to cancer disease. The second section is dedicated to the actual immune treatments including breast cancer vaccines, checkpoint inhibitors, monoclonal antibodies, and the “unconventional” immune role of chemotherapy.

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Immunotherapy: New insights in breast cancer treatment

Human Antibodies ◽

10.3233/hab-210443 ◽

2021 ◽

pp. 1-10

Author(s):

Bader Alshehri

Keyword(s):

Breast Cancer ◽

Immune Response ◽

Immune System ◽

Cancer Treatment ◽

Immune Evasion ◽

Breast Tumor ◽

Parp Inhibitor ◽

Breast Cancer Treatment ◽

New Treatment

Breast cancer being the most malignant and lethal disease persistent among women globally. Immunotherapy as a new treatment modality has emerged in understanding the loopholes in the treatment of breast cancer which is mainly attributed to the potential of tumor cells to evade and survive the immune response by developing various strategies. Therefore, improved understanding of the immune evasion by cancer cells and the monoclonal antibodies against PD- and PD-L1 can help us in the diagnosis of this malignancy. Here in this article, I have highlighted that in addition to focusing on other strategies for breast cancer treatment, the involvement of immune system in breast cancer is vital for the understanding of this malignancy. Further, the complete involvement of immune system in the relapse or recurrence of the breast tumor and have also highlighted the role of vaccines, PD-1 and CTLA-4 with the recent advances in the field. Moreover, in addition to the application of immunotherapy as a sole therapy, combinations of immunotherapy with various strategies like targeting it with MEK inhibitors, Vaccines, chemotherapy and PARP inhibitor has shown to have significant benefits is also discussed in this article.

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Molecular and Clinical Characterization of LAG3 in Breast Cancer Through 2994 Samples

10.21203/rs.3.rs-36422/v1 ◽

2020 ◽

Author(s):

Qiang Liu ◽

Yihang Qi ◽

Jie Zhai ◽

Xiangyi Kong ◽

Xiangyu Wang ◽

...

Keyword(s):

Breast Cancer ◽

Immune Response ◽

Cancer Immunotherapy ◽

Cancer Patients ◽

Immune Cell ◽

Immune Checkpoints ◽

Cell Populations ◽

Potential Biomarker ◽

The Impact

Abstract Background Despite the promising impact of cancer immunotherapy targeting CTLA4 and PD1/PDL1, a large number of cancer patients fail to respond. LAG3 (Lymphocyte Activating 3), also named CD233, is a protein Coding gene served as alternative inhibitory receptors to be targeted in the clinic. The impact of LAG3 on immune cell populations and co-regulation of immune response in breast cancer remained largely unknown. Methods To characterize the role of LAG3 in breast cancer, we investigated transcriptome data and associated clinical information derived from a total of 2994 breast cancer patients. Results We observed that LAG3 was closely correlated with major molecular and clinical characteristics, and was more likely to be enriched in higher malignant subtype, suggesting LAG3 was a potential biomarker of triple-negative breast cancer. Furthermore, we estimated the landscape of relationship between LAG3 and ten types of cell populations in breast cancer. Gene ontology analysis revealed LAG3 were strongly correlated with immune response and inflammatory activities. We investigated the correlation pattern between LAG3 and immune modulators in pan-cancer, especially the synergistic role of LAG3 with other immune checkpoints members in breast cancer. Conclusions LAG3 expression was closely related to malignancy of breast cancer and might serve as a potential biomarker; LAG3 might plays an important role in regulating tumor immune microenvironment, not only T cells, but also other immune cells. More importantly, LAG3 might synergize with CTLA4, PD1/ PDL1 and other immune checkpoints, thereby lending more evidences to combination cancer immunotherapy by targeting LAG3, PD1/PDL1, and CTLA4 together.

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The Role of the Tumor Microenvironment in Developing Successful Therapeutic and Secondary Prophylactic Breast Cancer Vaccines

Vaccines ◽

10.3390/vaccines8030529 ◽

2020 ◽

Vol 8 (3) ◽

pp. 529 ◽

Cited By ~ 1

Author(s):

Benjamin Gordon ◽

Vijayakrishna K. Gadi

Keyword(s):

Breast Cancer ◽

Tumor Microenvironment ◽

Cancer Vaccines ◽

Molecular Mechanisms ◽

New Combination ◽

Breast Carcinomas ◽

Therapeutic Vaccines ◽

Combination Strategies ◽

Disseminated Disease

Breast cancer affects roughly one in eight women over their lifetime and is a leading cause of cancer-related death in women. While outcomes have improved in recent years, prognosis remains poor for patients who present with either disseminated disease or aggressive molecular subtypes. Cancer immunotherapy has revolutionized the treatment of several cancers, with therapeutic vaccines aiming to direct the cytotoxic immune program against tumor cells showing particular promise. However, these results have yet to translate to breast cancer, which remains largely refractory from such approaches. Recent evidence suggests that the breast tumor microenvironment (TME) is an important and long understudied barrier to the efficacy of therapeutic vaccines. Through an improved understanding of the complex and biologically diverse breast TME, it may be possible to advance new combination strategies to render breast carcinomas sensitive to the effects of therapeutic vaccines. Here, we discuss past and present efforts to advance therapeutic vaccines in the treatment of breast cancer, the molecular mechanisms through which the TME contributes to the failure of such approaches, as well as the potential means through which these can be overcome.

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The Role of Breast Cancer Derived Prostaglandin E2 in the Elaboration of a Therapeutic Immune Response

10.21236/ada392455 ◽

2000 ◽

Author(s):

Stephen Eck

Keyword(s):

Breast Cancer ◽

Immune Response ◽

Prostaglandin E2

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Role of Activin A in Immune Response to Breast Cancer

10.21236/ada614021 ◽

2014 ◽

Author(s):

Claire I. Vanpouille-Box

Keyword(s):

Breast Cancer ◽

Immune Response ◽

Activin A

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Breast cancer: Role of tumor associated antigens and regulatory cells [CD4+CD25+] as targets of the Immune response elicited by an anti-progressive autologous hemoderivative vaccine

Journal of Clinical Oncology ◽

10.1200/jco.2005.23.16_suppl.2589 ◽

2005 ◽

Vol 23 (16_suppl) ◽

pp. 2589-2589 ◽

Cited By ~ 1

Author(s):

E. Garcia-Giralt ◽

E. Lasalvia-Prisco ◽

S. Cucchi ◽

J. Vázquez ◽

E. Lasalvia-Galante ◽

...

Keyword(s):

Breast Cancer ◽

Immune Response ◽

Regulatory Cells ◽

Tumor Associated Antigens

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ATIM-02. A NEW SOURCE OF NEOANTIGENS FOR PEDIATRIC AND ADULT BRAIN CANCER VACCINES

Neuro-Oncology ◽

10.1093/neuonc/noz175.002 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi1-vi1

Author(s):

Stephen Albert Johnston ◽

Milene Peterson ◽

Chris Diehnelt ◽

Luhui Shen

Keyword(s):

Breast Cancer ◽

Immune Response ◽

Brain Tumors ◽

Mouse Model ◽

Brain Cancer ◽

Cancer Vaccines ◽

Rich Source ◽

Adult Brain ◽

Tumor Type ◽

Therapeutic Vaccines

Abstract The paucity of mutations in pediatric and adult brain tumors has limited the ability to design therapeutic personal cancer vaccines. However, we have discovered that, in contrast to mutations in DNA, RNA is a rich source of frameshift neoantigens produced by mis-splicing of exons or indels from transcription through micro satellites. We have found that in GBM there are an average of 4000 such FS neoantigens per patient and in DIPG an average of at least 500 FS neoantigens/patient. Approximately 20% of these neoantigens are frequently recurrent across different patients. This has allowed us to design pre-synthesized vaccines for each tumor type. The vaccines consist of 20 -30 FS epitopes that are predicted to be present in at least 20% of all patient’s tumor. Each patient would have a 90% chance of having at least 50% of the peptides in their tumor. This type of “FAST” vaccine is much less expensive than a personal vaccine, any patient could be treated and there would be no delay in producing the vaccine. We have directly compared the efficacy of a FAST and personal vaccines in a mouse model of breast cancer. We find that both approaches have comparable protection though there are some interesting differences. We suggest that FAST vaccines may be a useful approach to developing therapeutic vaccines for brain cancers. We also demonstrate that an array of the 400K possible FS neoantigen peptides can be used to assay which neoantigens the patient has developed antibodies to. This array was useful in discovering the FAST vaccine components and could also be used to determine the pre-existing overlap of a FAST vaccine with the patient’s immune response.

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