Immunotherapy for the Treatment of Breast Cancer

Ernst, Brenda; Anderson, Karen S.

doi:10.1007/s11912-014-0426-9

Cited by 61 publications

(55 citation statements)

References 78 publications

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“…Targeted immune-based therapies hold great promise toward improving breast cancer treatments (6,7). Studies have examined the immune phenotype of breast cancer tumor-infiltrating lymphocytes (TILs), suggesting that activated nonsuppressive T cells are of most benefit (8).…”

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confidence: 99%

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Identification of shared TCR sequences from T cells in human breast cancer using emulsion RT-PCR

Munson

Egelston

Chiotti

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Infiltration of T cells in breast tumors correlates with improved survival of patients with breast cancer, despite relatively few mutations in these tumors. To determine if T-cell specificity can be harnessed to augment immunotherapies of breast cancer, we sought to identify the alpha-beta paired T-cell receptors (TCRs) of tumor-infiltrating lymphocytes shared between multiple patients. Because TCRs function as heterodimeric proteins, we used an emulsion-based RT-PCR assay to link and amplify TCR pairs. Using this assay on engineered T-cell hybridomas, we observed ∼85% accurate pairing fidelity, although TCR recovery frequency varied. When we applied this technique to patient samples, we found that for any given TCR pair, the dominant alpha-or beta-binding partner comprised ∼90% of the total binding partners. Analysis of TCR sequences from primary tumors showed about fourfold more overlap in tumor-involved relative to tumor-free sentinel lymph nodes. Additionally, comparison of sequences from both tumors of a patient with bilateral breast cancer showed 10% overlap. Finally, we identified a panel of unique TCRs shared between patients' tumors and peripheral blood that were not found in the peripheral blood of controls. These TCRs encoded a range of V, J, and complementarity determining region 3 (CDR3) sequences on the alpha-chain, and displayed restricted V-beta use. The nucleotides encoding these shared TCR CDR3s varied, suggesting immune selection of this response. Harnessing these T cells may provide practical strategies to improve the shared antigen-specific response to breast cancer.T-cell receptors | breast cancer | emulsion RT-PCR | high-throughput sequencing | T-cell repertoire profiling I nfiltration of numerous tumors by CD8 + alpha-beta T cells is associated with better outcomes and longer survival times for patients with breast cancer (1-5). Targeted immune-based therapies hold great promise toward improving breast cancer treatments (6, 7). Studies have examined the immune phenotype of breast cancer tumor-infiltrating lymphocytes (TILs), suggesting that activated nonsuppressive T cells are of most benefit (8). Further assessment of the TIL repertoire has broad implications for breast cancer therapies in antigen discovery, cancer vaccines, and adoptive cell therapies (7).Unique genetic recombination events are required to produce the T-cell receptor (TCR) (reviewed in 9). The alpha-and beta-chains of the TCR undergo V(D)J recombination and heterodimerize in the thymus, resulting in a diverse T-cell repertoire that specifically recognizes peptide-MHC complexes. Many studies have analyzed the alpha-and beta-chains of TIL TCRs separately using highthroughput sequencing to describe the diversity of TILs (10-13). Pairs are readily identified after expansion of T-cell clones, although culture of T cells can lead to substantial skewing of the repertoire (14), which may select for T cells of varied affinity or avidity (15). Single-cell sequencing identifies alpha-beta pairs, but is often laborious and has rela...

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confidence: 99%

“…Studies have examined the immune phenotype of breast cancer tumor-infiltrating lymphocytes (TILs), suggesting that activated nonsuppressive T cells are of most benefit (8). Further assessment of the TIL repertoire has broad implications for breast cancer therapies in antigen discovery, cancer vaccines, and adoptive cell therapies (7).…”

mentioning

confidence: 99%

Identification of shared TCR sequences from T cells in human breast cancer using emulsion RT-PCR

Munson

Egelston

Chiotti

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Recent immune based therapeutic approaches for cancer are: therapeutic cancer vaccines, cytokines, immune adjutants, immune checkpoint inhibitors and adoptive T cell therapy (ACT) (Wang et al, 2015;Ernst and Anderson, 2015). Therapeutic cancer vaccines contain a specific antigen expressed on tumor cell which may induce specific antitumor immune response of the patients through the introduction of tumor antigens (Rothschild et al, 2015;Hao et al, 2012;Schlom, 2012).…”

Section: Immunotherapies In Cancermentioning

confidence: 99%

Immune Checkpoint Inhibitors: Therapeutic Tools for Breast Cancer

Su¹,

Dai²

2016

Asian Pacific Journal of Cancer Prevention

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Breast cancer is one of the major threats to female health, and its incidence is rapidly increasing in many countries. Currently, breast cancer is treated with surgery, followed by chemotherapy or radiation therapy, or both. However, a substantial proportion of breast cancer patients might have a risk for local relapse that leads to recurrence of their disease and/or metastatic breast cancer. Therefore searching for new and potential strategies for breast cancer treatment remains necessary. Immunotherapy is an attractive and promising approach that can exploit the ability of the immune system to identify and destroy tumors and thus prevent recurrence and metastatic lesions. The most promising and attractive approach of immunotherapeutic research in cancer is the blockade of immune checkpoints. In this review, we discuss the potential of certain inhibitors of immune checkpoints, such as antibodies targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1) and lymphocyte activation gene-3 (LAG-3), in breast cancer therapeutics. Immune checkpoint inhibitors may represent future standards of care for breast cancer as monotherapy or combined with standard therapies.

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“…Antigen delivery is mostly combined with the co-administration of an adjuvant to enhance the response [37]. All of these current vaccine platforms have their advantages and limitations.…”

Section: Breast Cancer Vaccinesmentioning

confidence: 99%

“…However, results from a randomized trial in early breast cancer including 298 patients failed to demonstrate an improvement in DFS [42]. Clinical trials using long overlapping peptides derived from HER2 are also ongoing [37. ]…”

Section: Breast Cancer Vaccinesmentioning

confidence: 99%

Immunotherapy in Breast Cancer

Marmé¹

2016

Oncol Res Treat

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The importance of the tumor microenvironment including immune cell infiltrates in breast cancer has long been recognized. Tumor-infiltrating lymphocytes are prognostic and predictive; however, their prevalence as well as their prognostic and predictive power are subtype-dependent and appear most prominent in aggressive subtypes like triple-negative and HER2-positive disease. The immune responses observed in many cancers are attracted by tumor-associated antigens and, as suggested by recent research, by neoantigens - immunogenic antigens encoded for by non-synonymous mutations. The appealing promise of cancer vaccines has been pursued in breast cancer for over 2 decades; however, despite much effort having been put into vaccine trials, their clinical benefit, with the exception of some encouraging preliminary results, remains disappointing. The main hurdles compromising the efficacy of these vaccination strategies are the difficulties to generate broad and robust immune responses as well as to overcome immune escape mechanisms. The remarkable efficacy of immune checkpoint inhibitors in melanoma and lung cancer has set the ground for a race in the clinical development of numerous agents targeting these immune escape mechanisms in many tumor entities. Early clinical data in metastatic breast cancer suggests at least some clinical activity. This review discusses the current status and future perspectives of immunotherapy in breast cancer.

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Immunotherapy for the Treatment of Breast Cancer

Cited by 61 publications

References 78 publications

Identification of shared TCR sequences from T cells in human breast cancer using emulsion RT-PCR

Identification of shared TCR sequences from T cells in human breast cancer using emulsion RT-PCR

Immune Checkpoint Inhibitors: Therapeutic Tools for Breast Cancer

Immunotherapy in Breast Cancer

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