abscopal effect

PURPOSE: Radiotherapy (RT) is a widely employed anti-cancer treatment. Emerging evidence suggests that RT can elicit both tumor-inhibiting and tumor-promoting immune effects. This study is to investigate immune suppressive factors of radiotherapy. EXPERIMENTAL DESIGN: We used a heterologous two-tumor model in which adaptive concomitant immunity was eliminated. RESULTS: Through analysis of PD-L1 expression and MDSC frequencies using patient PBMC and murine two-tumor and metastasis model, we report that local irradiation can induce a systemic increase in MDSCs, as well as PD-L1 expression on DCs and myeloid cells, and thereby increase the potential for metastatic dissemination in distal, non-irradiated tissue...

Immune checkpoint inhibitor (ICI) therapy is effectively employed in treating various malignancies. However, the response rate is constrained to 5-30%, which is attributed to differences in immune responses across different tumors. Overcoming all obstacles of multistep immune activation with monotherapy is difficult. Here, maleimide-modified resiquimod (R848) prodrug nanoparticles (MAL-NPs) are reported and combined with radiotherapy (RT) and anti-PD1 to enhance ICI therapy. MAL-NPs can promote antigen endocytosis by dendritic cells and are radio-reduced to produce R848...

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...

Immunotherapy has emerged as an innovative strategy with the potential to improve outcomes in cancer patients. Recent evidence indicates that radiation-induced DNA damage can activate the cGAS-STING pathway to enhance the antitumor immune response. Even so, only a small fraction of patients currently benefits from radioimmunotherapy due to the radioresistance and the inadequate activation of the cGAS-STING pathway. Herein, we integrated HfO2 nanoparticles (radiosensitizer) and SN38 (chemotherapy drug, STING agonist) into a polydopamine-coated core-shell nanoplatform (HfO2 @PDA/Fe/SN38) to achieve synergistic chemoradiotherapy and immunotherapy...

Cytokines are powerful in cancer immunotherapy, however, their therapeutic potential has been limited by the severe systemic toxicity. Here we describe a potent strategy to reduce the toxicity of systemic cytokine therapy by delivering its denatured form using a finely designed nanochaperone. We demonstrate that even if the denatured protein cargos are occasionally released under normal physiological conditions they are still misfolded, while can effectively refold into native states and release to fuction in tumor microenvironment...

Cancer progression and treatment-associated cellular stress impairs therapeutic outcome by inducing resistance. Endoplasmic reticulum (ER) stress is responsible for core events. Aberrant activation of stress sensors and their downstream components to disrupt homeostasis have emerged as vital regulators of tumor progression as well as response to cancer therapy. Here, an orchestrated nanophotoinducer (ERsNP) results in specific tumor ER-homing, induces hyperthermia and mounting oxidative stress associated reactive oxygen species (ROS), and provokes intense and lethal ER stress upon near-infrared laser irradiation...

Irreversible Electroporation (IRE) is a non-thermal tumor ablation technique. High-voltage electrical pulses are applied between pairs of electrodes inserted around and/or inside a tumor. The generated electric current induces the creation of nanopores in the cell membrane, triggering apoptosis. As a result, IRE can be safely used in areas near delicate vascular structures where other thermal ablation methods are contraindicated. Currently, IRE has demonstrated to be a successful ablation technique for pancreatic, renal, and liver tumors and is widely used as a focal therapeutic option for prostate cancer...

Due to the increasing incidence of cancer, there is a need to develop new platforms that can combat this disease. Cancer immunotherapy is a platform that takes advantage of the immune system to recognize and eradicate tumors and metastases. Our lab has identified a plant virus nanoparticle, cowpea mosaic virus (CPMV) as a promising approach for cancer immunotherapy. When administered intratumorally, CPMV relieves the immune system of tumor-induced immunosuppression and reprograms the tumor microenvironment into an activated state to launch systemic antitumor immunity...

BACKGROUND: The abscopal effect is a rare phenomenon in which localized radiation therapy triggers tumor reduction in nontargeted areas. Although this phenomenon has been observed in various cancer types, it remains infrequent and not fully understood. CASE: Two patients with maxillary sinus cancer with distant metastases were treated with radiotherapy after immune checkpoint inhibitor (ICI) therapy. The patients demonstrated abscopal effects following ICI therapy and radiotherapy, showing shrinkage in metastatic areas not directly targeted by radiation...

Cancer immunotherapy is expected to achieve tumor treatment mainly by stimulating the patient's own immune system to kill tumor cells. However, the low immunogenicity of the tumor and the poor efficiency of tumor antigen presentation result in a variety of solid tumors that do not respond to immunotherapy. Herein, we designed a proton-gradient-driven porphyrin-based liposome (PBL) with highly efficient Toll-like receptor 7 (TLR7) agonist (imiquimod, R837) encapsulation (R837@PBL). R837@PBL rapidly released R837 in the acid microenvironment to activate the TLR in the endosome inner membrane to promote bone-marrow-derived dendritic cell maturation and enhance antigen presentation...

Systemic drug delivery is the current clinically preferred route for cancer therapy. However, challenges associated with tumor localization and off-tumor toxic effects limit the clinical effectiveness of this route. Locoregional drug delivery is an emerging viable alternative to systemic therapies. With the improvement in real-time imaging technologies and tools for direct access to tumor lesions, the clinical applicability of locoregional drug delivery is becoming more prominent. Theoretically, locoregional treatments can bypass challenges faced by systemic drug delivery...

Interest surrounding the effect of irradiation on immune activation has exponentially grown within the last decade. This includes work regarding mechanisms of the abscopal effect and the success achieved by combination of radiotherapy and immunotherapy. It is hypothesized that irradiation triggers the immune system to eliminate tumors by inducing tumor cells immunogenic cell death (ICD) in tumor cells. Activation of the ICD pathways can be exploited as an in situ vaccine. In this review, we provide fundamental knowledge of various forms of ICD caused by irradiation, describe the relationship between various cell death pathways and the immune activation effect driven by irradiation, and focus on the therapeutic value of exploiting these cell death programs in the context of irradiation...

Near-infrared photoimmunotherapy(NIR-PIT)is a novel cancer treatment modality that employs antibody-IRDye700DX (IR700)conjugates. Recently, the clinical application of NIR-PIT has received approval in Japan for patients with inoperable head and neck cancer, specifically targeting the human epidermal growth factor receptor(hEGFR). Furthermore, NIR-PIT extends beyond the scope of tumor antigens and can be employed to eliminate specific host cells that contribute to the creation of immune-permissive environments supporting tumor growth...

Microwave ablation (MWA) is a key alternative therapy to conventional surgery for the treatment of lung cancer. In addition to eliminating local tumors, MWA may promote antitumor immunological responses, such as abscopal effects in distant lesions. However, the intensity of MWA is limited and the underlying mechanisms are not well-defined. The present study assessed the impact of MWA on immune cell subsets and cytokines in patients with lung cancer. A total of 45 patients with lung cancer who underwent percutaneous lung tumor MWA were enrolled...

Immune checkpoint inhibitors help treat malignant melanoma, but show limited use in treating malignant vaginal melanoma, an aggressive, rare gynecological malignancy. We identified two patients treated with ipilimumab and nivolumab for vaginal melanoma; both were immunonegative for programmed cell death-ligand 1 and wild-type BRAF. Case 1, a 56-year-old female who underwent radical surgery for stage 1 malignant vaginal melanoma, experienced recurrence 15 months postoperatively. She briefly responded to ipilimumab and nivolumab combination therapy before showing disease progression...

Radiotherapy (RT) can induce tumor regression outside the irradiation field, known as the abscopal effect. However, the detailed underlying mechanisms remain largely unknown. A tumor-bearing mouse model is successfully constructed by inducing both subcutaneous tumors and lung metastases. Single-cell RNA sequencing, immunofluorescence, and flow cytometry are performed to explore the regulation of tumor microenvironment (TME) by RT. A series of in vitro assays, including luciferase reporter, RNA Pulldown, and fluorescent in situ hybridization (FISH) assays, are performed to evaluate the detailed mechanism of the abscopal effect...

Diffuse large B-cell lymphoma (DLBCL) of the skull is rare, and there are no reports of treatment using CyberKnife (CK). Here, we report the case of a patient with skull DLBCL treated with low-dose CK radiotherapy (CKR), resulting in effective local control. The patient was a 75-year-old man who was initially diagnosed with multiple skull metastases (frontal, occipital, right orbital bones) from renal pelvic cancer. We initially created a CKR treatment plan for the frontal bone lesion with a marginal dose of 35 Gy and a maximum of 64...

BACKGROUND: Cryoablation is a minimally invasive option for patients with medically inoperable non-small cell lung cancer (NSCLC) and can trigger abscopal immune-regulatory effects. However, it remains unclear how cryoablation affects the host-level immune response in NSCLC. In this study, we investigated the local and systemic immunological effects of cryoablation and the potential of combining cryoablation with programmed cell death protein 1 (PD-1) blockade to boost immunotherapy efficacy in NSCLC...

Targeting multiple immune mechanisms may overcome therapy resistance and further improve cancer immunotherapy for humans. Here, we describe the application of virus-like vesicles (VLV) for delivery of three immunomodulators alone and in combination, as a promising approach for cancer immunotherapy. VLV vectors were designed to deliver single chain interleukin (IL)-12, short-hairpin RNA (shRNA) targeting programmed death ligand 1 (PD-L1), and a dominant-negative form of IL-17 receptor A (dn-IL17RA) as a single payload or as a combination payload...

We present the case of a patient who was diagnosed in 2018 with nodular Malignant Melanoma (MM) without BRAF V 600 mutations stage 3 C (pT4b pN1a M0), and who underwent adjuvant citokines treatment with Interferon alpha 2b-48 weeks. Immunotherapy was initiated in January 2021 for lung and lymph node metastases. In June 2021, there was a partial response of the lung and lymph node metastases, but there was also progression to brain metastases. Immunotherapy was continued and Whole Brain Radiotherapy (WBRT) was performed...