Immunotherapy in Triple-Negative Breast Cancer: Present and Future

Kim, Isaac; Sanchez, Katherine; McArthur, Heather L.; Page, David B.

doi:10.1007/s12609-019-00345-z

Cited by 27 publications

(25 citation statements)

References 86 publications

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“…High levels of these proteins in poor responders to chemotherapy suggest that these may be responsive to immunotherapy. Despite disappointing results of breast cancer response to single-agent immunotherapy, recent clinical trials suggest higher response of triple-negative tumors in combination with chemotherapy (Kim et al, 2019;Planes-Laine et al, 2019). Our results suggest that these approaches may also be applicable to aggressive ER + tumors that do not respond to neoadjuvant therapy.…”

Section: Discussionmentioning

confidence: 70%

Proteomic patterns associated with response to breast cancer neoadjuvant treatment

Shenoy

Nataraj

Perry

et al. 2020

Molecular Systems Biology

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Tumor relapse as a consequence of chemotherapy resistance is a major clinical challenge in advanced stage breast tumors. To identify processes associated with poor clinical outcome, we took a mass spectrometry‐based proteomic approach and analyzed a breast cancer cohort of 113 formalin‐fixed paraffin‐embedded samples. Proteomic profiling of matched tumors before and after chemotherapy, and tumor‐adjacent normal tissue, all from the same patients, allowed us to define eight patterns of protein level changes, two of which correlate to better chemotherapy response. Supervised analysis identified two proteins of proline biosynthesis pathway, PYCR1 and ALDH18A1, that were significantly associated with resistance to treatment based on pattern dominance. Weighted gene correlation network analysis of post‐treatment samples revealed that these proteins are associated with tumor relapse and affect patient survival. Functional analysis showed that knockdown of PYCR1 reduced invasion and migration capabilities of breast cancer cell lines. PYCR1 knockout significantly reduced tumor burden and increased drug sensitivity of orthotopically injected ER‐positive tumor in vivo, thus emphasizing the role of PYCR1 in resistance to chemotherapy.

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Section: Discussionmentioning

confidence: 70%

Proteomic patterns associated with response to breast cancer neoadjuvant treatment

Shenoy

Nataraj

Perry

et al. 2020

Molecular Systems Biology

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“…Furthermore, TIL count is associated with improved survival, reduced recurrence risk, and augmented probability of response to neoadjuvant chemotherapy in early-stage TNBC [ 4 ]. These and other characteristics make TNBC patients proper candidates for immunotherapy [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Cetuximab and IL-15 Promote NK and Dendritic Cell Activation In Vitro in Triple Negative Breast Cancer

Juliá¹,

Mordoh

Levy³

2020

Cells

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Triple Negative Breast Cancer (TNBC) treatment is still challenging, and immunotherapy is a potential approach in this tumor subtype. Cetuximab is an IgG1 monoclonal antibody (mAb) directed against Epidermic Growth Factor Receptor (EGFR), a protein overexpressed in a subgroup of TNBC patients and associated with poor prognosis. Previously, we demonstrated in vitro that Cetuximab triggers Ab-dependent cell cytotoxicity against TNBC cells. In this study, using co-cultures including TNBC cells, and NK and Dendritic Cells (DCs) from healthy donors, we studied the effect of Cetuximab-activated NK cells on DC function. Given that we already demonstrated that TNBC has an immunosuppressive effect on NK cells, we also tested Cetuximab combination with IL-15. We determined that Cetuximab opsonization of TNBC cells increased IFN-γ and TNF-α production by NK cells co-cultured with DCs. Moreover, we showed that NK cells activated by TNBC cells opsonized with Cetuximab promoted tumor material uptake and maturation of DCs, as well as their ability to produce IL-12. Furthermore, the stimulation with IL-15 increased the activation of NK cells and the maturation of DCs. These results suggest that IL-15 may enhance the efficacy of Cetuximab in the treatment of TNBC by promoting activation of both NK cells and DCs.

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“…Similar conflicting findings have been reported for the combination of atezolizumab with different agents, such as nab-paclitaxel and paclitaxel, for the treatment of metastatic disease [ 41 ]. As in the metastatic setting, many RCTs are currently being conducted to evaluate the therapeutic efficacy of IC inhibitors used in combination with anticancer agents in the neoadjuvant and partially adjuvant settings [ 42 , 43 ]. The effects of different combinations of anticancer agents and IC inhibitors remain confusing due to discrepancies among trial results.…”

Section: Induction Of Antitumor Immunity After Neoadjuvant and Adjmentioning

confidence: 99%

Clinical Perspectives in Addressing Unsolved Issues in (Neo)Adjuvant Therapy for Primary Breast Cancer

Kim¹,

Kin

2021

Cancers

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The treatment of primary breast cancer has evolved over the past 50 years based on the concept that breast cancer is a systemic disease, with the escalation of adjuvant and neoadjuvant therapies and de-escalation of breast cancer surgery. Despite the development of these therapies, recurrence with distant metastasis during the 10 years after surgical treatment is observed, albeit infrequently. Recent advances in genomic analysis based on circulating tumor cells and circulating tumor DNA have enabled the development of targeted therapies based on genetic mutations in residual tumor cells. A paradigm shift involving the application of neoadjuvant chemotherapy (NAC) has enabled the prediction of treatment response and long-term prognoses; additional adjuvant chemotherapy targeting remaining tumor cells after NAC improves survival. The activation of antitumor immunity by anticancer agents may be involved in the eradication of residual tumor cells. Elucidation of the manner in which antitumor immunity is induced by anticancer agents and unknown factors, and the overcoming of drug resistance via the targeted eradication of residual tumor cells based on genomic profiles, will inevitably lead to the achievement of 0% distant recurrence and a complete cure for primary breast cancer.

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Immunotherapy in Triple-Negative Breast Cancer: Present and Future

Cited by 27 publications

References 86 publications

Proteomic patterns associated with response to breast cancer neoadjuvant treatment

Proteomic patterns associated with response to breast cancer neoadjuvant treatment

Cetuximab and IL-15 Promote NK and Dendritic Cell Activation In Vitro in Triple Negative Breast Cancer

Clinical Perspectives in Addressing Unsolved Issues in (Neo)Adjuvant Therapy for Primary Breast Cancer

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