&lt;p&gt;Combination Strategies of Checkpoint Immunotherapy in Metastatic Breast Cancer&lt;/p&gt;

Liu, Zhi Bing; Zhang, Luyan; Ji, Bing; Jian, Jinbo

doi:10.2147/ott.s240655

Cited by 11 publications

(7 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, recent studies discovered that radiation might have broader systemic effects. There is a theory that radiotherapy induced cancer necrosis and any endogenous cancer specific antigens exposed may lead to innate immune response, called an abscopal effect, and result in distant cancer remission ( 23 – 26 ). This will strengthen the theoretical foundation for performing radiotherapy for dnMBC patients.…”

Section: Discussionmentioning

confidence: 99%

Impact of Postoperative Radiotherapy on Survival of Patients With de novo Stage IV Breast Cancer: A Population-Based Study From the SEER Database

et al. 2021

View full text Add to dashboard Cite

Purpose: In our study, we aimed to evaluate the role of postoperative radiotherapy for patents with de novo stage IV breast cancer.Patients and Methods: Patients diagnosed with stage IV breast cancer from 2010 to 2016 were selected from the Surveillance, Epidemiology, and End Result (SEER) database. Those patients who received both chemotherapy and surgery and lived longer than 6 months were divided into radiotherapy and non-radiotherapy groups. Kaplan-Meier analysis and multivariate Cox proportional hazards models were used to estimate the survival outcomes before and after being 1:1 propensity score matched (PSM). Subgroup analyses stratified by age, subtype, status of distant metastasis, and surgery type were also performed.Results: Among 1,935 patients, 52% (1006) underwent radiotherapy while the non-radiotherapy group contained 48% (929). After PSM, a total of 1,520 patients in two groups of 760 patients were enrolled in this analysis. Kaplan-Meier and the multivariate survival analysis demonstrated that the radiotherapy group presented with a better prognosis compared to the non-radiotherapy group (after PSM, BCSS: Hazard Ratio, 0.697; 95% confidence interval, 0.59–0.823; P < 0.001; OS: Hazard Ratio, 0.707; 95% confidence interval, 0.601–0.831; P < 0.001). Further subgroup analyses showed the Luminal subtype (HR+/HER2–), triple-negative breast cancer (TNBC), and bone-only metastasis patients presented with the most promising survival in the radiotherapy group.Conclusions: Postoperative radiotherapy is associated with a significant survival advantages in BCSS and OS. It can be an optimal supplementary treatment for stage IV patients after surgery, especially for Luminal subtype, TNBC, and patients with a low metastatic burden.

show abstract

Section: Discussionmentioning

confidence: 99%

Impact of Postoperative Radiotherapy on Survival of Patients With de novo Stage IV Breast Cancer: A Population-Based Study From the SEER Database

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Recently, considering the benefits of combinatorial treatments of anti-PD-1 and anti-CTLA-4 monoclonal antibodies, such as nivolumab and ipilimumab, in many types of cancer [ 23 , 24 ] a small pilot study was carried out also on TNBC, highlighting a positive response in 16.7% of patients when they were treated with the anti-PD-L1 durvalumab and the anti-CTLA-4 mAb tremelimumab [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Combinations of Human Immunomodulatory mAbs Lacking Cardiotoxic Effects for Therapy of TNBC

Vetrei

Passariello

Froechlich

et al. 2021

Cancers

View full text Add to dashboard Cite

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer characterized by a higher mortality rate among breast cancer subtypes. Poly(ADP-ribose) polymerase (PARP) inhibitors are used in clinics to treat a subgroup of TNBC patients, but other targeted therapies are urgently needed. Programmed death-ligand 1 (PD-L1), involved in tumor immune escape, was recently identified as a target for TNBC; accordingly, the anti-PD-L1 monoclonal antibody (mAb), atezolizumab, has been approved by FDA in combination with Paclitaxel for the therapy of metastatic TNBC. Here, we tested novel combinations of fully human immunomodulatory mAbs, including anti-PD-L1 mAbs generated in our laboratory and atezolizumab, on TNBC and other tumor cell lines. We evaluated their anti-tumor efficacy when used as single agents or in combinatorial treatments with anti-CTLA-4 mAbs in in vitro co-cultures of hPBMCs with tumor cells, by measuring tumor cell lysis and IL-2 and IFNγ cytokines secretion by lymphocytes. In parallel, by using co-cultures of hPBMCs and cardiomyocytes, we analyzed the potential cardiotoxic adverse side effects of the same antibody treatments by measuring the cardiac cell lysis and the secretion of pro-inflammatory cytokines. We identified novel combinations of immunomodulatory mAbs endowed with more potent anti-cancer activity on TNBC and lower cardiotoxic side effects than the combination of atezolizumab and ipilimumab.

show abstract

“…The efficacy of immunomodulatory antibodies might be compromised when used as single agents, owing to different immune escape mechanisms [ 2 ], such as lack of tumor immunogenicity, suppressive tumor microenvironment, compensatory upregulation of other ICs, immunoediting, T cells permanent exhaustion and others [ 16 , 17 , 18 , 19 , 20 ]. Consequently, a large number of clinical trials have begun over the recent years in order to adopt combinatorial therapies in a wide range of cancers, which have shown remarkable improvements in overall response and clinical benefits, when compared to monotherapies [ 3 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. However, on the other side, an enhancement of immune-related adverse effects (irAEs) has also been reported in several cases of patients treated with combinations of immune checkpoint inhibitors [ 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

“…Breast cancer is the most common type of cancer in women, displaying a wide heterogeneity at a molecular level, thereby having different clinical outcomes [ 30 ]. Specifically, triple-negative breast cancer (TNBC) shows not only an extremely aggressive and invasive phenotype but also resistance to the most common therapies currently approved for non-TNBC breast cancer, being one of the most challenging tumors to treat [ 23 , 24 , 25 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

New Insights on the Role of Anti-PD-L1 and Anti-CTLA-4 mAbs on Different Lymphocytes Subpopulations in TNBC

Lembo

Manna

Froechlich

et al. 2022

Cancers

View full text Add to dashboard Cite

Antibody-based cancer immunotherapy includes monoclonals against immune checkpoints (ICs), to modulate specific T cell responses against cancer. NK cells are a newly emerging target for immune checkpoint receptor inhibition in cancer immunotherapy, as ICs are also expressed on NK cells in various cancers. The latter cells are becoming attractive targets for cancer immunotherapy, as they are effector cells similar to CTLs, exerting natural cytotoxicity against primary tumor cells and metastasis, and they are able to distinguish tumor cells from healthy ones, leading to more specific anti-tumor cytotoxicity and reduced off-target effects. Thus, we decided to test the effects on isolated NK cells and T cell subpopulations of novel immunomodulatory mAbs, recently generated in our lab, in comparison with those in clinical use, such as ipilimumab and atezolizumab. Interestingly, we found that the novel anti-CTLA-4 (ID-1) and anti-PD-L1 (PD-L1_1) antibodies are able to induce NK cell activation and exert anti-tumor effects on TNBC cells co-cultured with NK cells more efficiently than the clinically validated ones, either when used as single agents or in combinatorial treatments. On the other hand, ipilimumab was found to be more effective in activating T cells with respect to ID-1. These findings indicate that antibodies targeting different epitopes can have differential effects on different lymphocytes subpopulations and that novel combinations of mAbs could be suitable for therapeutic approaches aimed at activating not only T cells but also NK cells, especially for tumors lacking MHC.

show abstract

<p>Combination Strategies of Checkpoint Immunotherapy in Metastatic Breast Cancer</p>

Cited by 11 publications

References 64 publications

Impact of Postoperative Radiotherapy on Survival of Patients With de novo Stage IV Breast Cancer: A Population-Based Study From the SEER Database

Impact of Postoperative Radiotherapy on Survival of Patients With de novo Stage IV Breast Cancer: A Population-Based Study From the SEER Database

Novel Combinations of Human Immunomodulatory mAbs Lacking Cardiotoxic Effects for Therapy of TNBC

New Insights on the Role of Anti-PD-L1 and Anti-CTLA-4 mAbs on Different Lymphocytes Subpopulations in TNBC

Contact Info

Product

Resources

About