abscopal breast cancer

PURPOSE: Breast cancer treatments are based on prognostic clinicopathological features that form the basis for therapeutic guidelines. While the utilization of these guidelines has decreased breast cancer-associated mortality rates over the past three decades, they are not adequate for individualized therapy. Radiation therapy (RT) is the backbone of breast cancer treatment. Although a highly successful therapeutic modality clinically, from a biological perspective, preclinical studies have shown RT to have the potential to alter tumor cell phenotype, immunogenicity and the surrounding microenvironment, potentially changing the behavior of cancer cells and resulting in a significant variation in RT response...

Immunotherapy utilizing anti-PD-L1 blockade has achieved dramatic success in clinical breast cancer management but is often hampered by the limited immune response. Increasing evidence shows that immunogenic cell death (ICD) recently arises as a promising strategy for enlarging tumor immunogenicity and eliciting systemic anti-tumor immunity effectively. However, developing simple but versatile, highly efficient but low-toxic, biosafe, and clinically available transformed ICD inducers remains a huge demand and is highly desirable...

PURPOSE: This study aimed to provide a novel noninvasive method to quantify abscopal immune activation and predict combinational treatment response using [68 Ga]-NOTA-GZP positron emission tomography (PET) imaging. METHODS AND MATERIALS: 4T1 breast cancer cells were implanted bilaterally in the mammary fat pad of Balb/c mice and Lewis's lung cancer cells (LLC) were implanted bilaterally on the shoulders of C57/Bl6 mice. One of the tumors received a single fraction of 12 Gy irradiation followed by combination of concurrent PD-1 and CTLA-4 inhibitors or controls...

PURPOSE: In the past decade, immune checkpoint inhibitors (ICIs) have emerged as a treatment option for metastatic breast cancer (BC). More recently, ICIs have been approved in the perioperative setting. This has led to clinical scenarios where radiation therapy (RT) is given concurrently with ICIs. On the other hand, moderate and ultrahypofractionated schedules of RT are being widely adopted in the adjuvant setting, in addition to an increased use of metastasis-directed therapy. Furthermore, RT can modulate the tumor microenvironment and induce a systemic response at nonirradiated sites, an "abscopal effect...

PURPOSE: This study compares the immune response and survival following size-matched Radiofrequency (RFA) and a proprietary form of Pulsed Electric Field (PEF) ablation in murine tumors. MATERIAL AND METHODS: Orthotopically inoculated EMT6 or 4T1 murine tumors received Sham, RFA, or PEF ablation. 4T1 tumor ablations included subgroups with checkpoint inhibition immunotherapy (αPD-1) administered intraperitoneally. Blood was collected for cytokine profiling and flow cytometry...

Percutaneous cryoablation is a common clinical therapy for metastatic and primary cancer. There are rare clinical reports of cryoablation inducing regression of distant metastases, known as the "abscopal" effect. Intratumoral immunoadjuvants may be able to augment the abscopal rate of cryoablation, but existing intratumoral therapies suffer from the need for frequent injections and inability to confirm target delivery, leading to poor clinical trial outcomes. To address these shortcomings, we have developed an injectable thermoresponsive gel-based controlled release formulation for the FDA-approved TLR7 agonist imiquimod ("Imigel") that forms a tumor-resident depot upon injection and contains a contrast agent for visualization under CT...

PURPOSE: In this study, we aimed to assess the abscopal effect (AE) after CyberKnife stereotactic body radiotherapy (SBRT) in metastatic breast cancer patients without immunotherapy. METHODS: We reviewed breast cancer patients who received SBRT with a fraction size of ≥ 6 Gy for metastatic lesions between July 2008 and December 2021. We selected patients who had at least one measurable extracranial lesion in addition to SBRT target lesions and were not treated with immunotherapy...

Breast cancer is the second most common cancer among women in the United States in which the standard of care treatment is surgery with adjunctive therapy. Cryoablation, which destroys the tumor using extremely cold temperatures while preserving the potential tumor antigens, is a promising alternative to surgical resection. It is less invasive, cosmetically appeasing, cost-effective, and capable of contributing to the abscopal effect - the immune response targeting potential distant metastasis. However, to maximize the immunologic benefit of cryoablation in biologically high-risk breast cancers, combination with therapies that enhance immune activation, such as immune checkpoint inhibitors (ICIs) may be necessary...

BACKGROUND AND PURPOSE: This study tested the hypothesis that a novel combination of stereotactic ablation radiotherapy (SABR) and a cancer vaccine against fibroblast activation protein-alpha (FAPα) can suppress established tumor growth and impede potential metastasis. METHODS: The poorly immunogenic metastatic mouse mammary carcinoma 4T1 was used as a model. Mice were randomly assigned to five treatment groups: (1) untreated control, (2) FAPα-based cancer vaccine, (3) SABR, (4) SABR + pCDH (lentiviral control vector), (5) SABR + FAPα-based cancer vaccine (SABR/FAPα-Vax)...

PURPOSE/OBJECTIVE(S): To identify predictive biomarkers for combined radiotherapy (RT) and immune checkpoint inhibitor (ICI) therapy, which can induce systemic anti-tumor immune responses (i.e., "abscopal" responses) in breast cancer. MATERIALS/METHODS: Four Trp53-/- Balb/c breast cancer syngeneic allograft models with low tumor mutational burden and resistance to dual ICI (anti-PD1 and anti-CTLA4, BioXcell) were used. Two lines exhibited abscopal responses to RT (8Gyx3) plus ICI combination therapy (i...

Pharmacological activation of stimulator of interferon genes (STING) pathway has become a promising strategy for cancer immunotherapy, however, the insufficient tumorous accumulation, rapid clearance, and short duration of drug efficacy in the tumor microenvironment (TME) of small structural STING agonists greatly compromise the therapeutic efficacy. Herein, we present a tumorous extracellular matrix (ECM) anchoring STING agonist-based photoimmunothernostic nanomedicine (SAPTN) that can be activated by mild-temperature photothermal therapy (mild PTT) induced neutrophilic inflammation...

Bromodomain-containing protein 4 (BRD4) is an intracellular protein that regulates expression of various cellular functions. This study investigated whether BRD4 inhibition can alter the immunomodulatory and antitumor effects of radiation therapy (RT). A murine breast cancer cell line was implanted into BALB/c mice. The dual-tumor model was used to evaluate the abscopal effects of RT. A total of 24 Gy was delivered and BRD4 inhibitor was injected intravenously. Tumor size was measured, and in vivo imaging was performed to evaluate tumor growth...

Irradiation (IR) induces immunogenic cell death (ICD) in tumors, but it rarely leads to the abscopal effect (AE). However, combining IR with immune checkpoint inhibitors has shown anecdotal success in inducing AEs. In this study, we aimed to enhance the IR-induced immune response and generate reproducible AEs using the anti-alcoholism drug disulfiram (DSF) and copper complex (DSF/Cu) via induction of tumor ICD. We measured ICD in vitro and in vivo. In mouse tumor models, DSF/Cu was injected intratumorally followed by localized tumor IR, creating an in situ cancer vaccine...

This preliminary study seeks to determine the effect of R&P denervation on tumor growth and survival in immunocompetent rats bearing an aggressive and metastatic breast solid tumor. A novel microsurgical approach was applied "in situ", aiming to induce R&P denervation through the division of every single nerve fiber connecting the host with the primary tumor via its complete detachment and re-attachment, by resecting and reconnecting its supplying artery and vein (anastomosis). This preparation, known as microsurgical graft or flap, is radically denervated by definition, but also effectively delays or even impedes the return of innervation for a significant period of time, thus creating a critical and therapeutic time window...

Triple-negative breast cancer (TNBC) is one of the most aggressive cancers with an immunosuppressive microenvironment, and achieving a satisfactory effect from monotherapies, such as chemotherapy, photodynamic therapy (PDT) or immunotherapy, remains difficult. To solve this puzzle, a deepening synergistic therapy strategy of DNA damage and immunogenic cell death (ICD) stimuli was proposed. We engineered a doxorubicin (DOX) and 4-(hydroxymethyl) phenylboronic acid pinacol ester (PBAP) prodrug polymer, and encapsulated chlorin e6 (Ce6) to obtain the hyaluronidase (HAase) and H2 O2 dual-sensitive responsive nanoparticles (Ce6/HDP NPs)...

INTRODUCTION: Sonodynamic therapy (SDT) as an emerging tumor treatment gained wide attention. However, tumor vascular destruction and oxygen depletion in SDT process may lead to further hypoxia. This may lead to enhanced glycolysis, lactate accumulation, and immunosuppression. METHODS: A glycolysis inhibitor (3PO) loaded and PEG modified black phosphorus nanosheets (BO) is constructed for potent starvation therapy and efficient immune activation. RESULTS: Under ultrasound irradiation, the BO can produce ROS to destroy tumors and tumor blood vessels and lead to further hypoxia and nutrients block...

BACKGROUND: Breast cancer is one of the most common malignancies worldwide and remains incurable after metastasis, with a 3-year overall survival rate of <40%. CASE PRESENTATION: A 40-year-old, Caucasian patient with a grade-3 estrogen receptor-, progesterone receptor-, Her2-positive breast tumor and two lung nodules was treated with intramuscular targeted immunotherapy with trastuzumab and oral tamoxifen hormone therapy, together with customized intra-tumoral oncolytic virotherapy (IT-OV) over a 17-month period...

BACKGROUND: The malaria protein VAR2CSA binds oncofetal chondroitin sulfate (ofCS), a unique chondroitin sulfate, expressed on almost all mammalian cancer cells. Previously, we produced a bispecific construct targeting ofCS and human T cells based on VAR2CSA and anti-CD3 (V-aCD3Hu ). V-aCD3Hu showed efficacy against xenografted tumors in immunocompromised mice injected with human immune cells at the tumor site. However, the complex effects potentially exerted by the immune system as a result of the treatment cannot occur in mice without an immune system...

INTRODUCTION: Immunotherapy (IT) is showing promise in the treatment of breast cancer, but IT alone only benefits a minority of patients. Radiotherapy (RT) is usually included in the standard of care for breast cancer patients and is traditionally considered as a local form of treatment. The emerging knowledge of RT-induced systemic immune response, and the observation that the rare abscopal effect of RT on distant cancer metastases can be augmented by IT, have increased the enthusiasm for combinatorial immunoradiotherapy (IRT) for breast cancer patients...

While breast cancer is a common disease with many available treatment options, many patients still have limited responses, especially those with metastatic breast cancer. Surgery of the primary tumor or metastatic sites is often not part of the treatment regimen for patients with metastatic breast cancer. Cryoablation is a relatively non-invasive procedure that is being investigated for patients with breast cancer. Patients with metastatic breast cancer who are not surgical candidates may derive benefit from cryoablation through the abscopal effect...