The use of immunomodulation to treat malignancies has seen a recent explosion in interest. The therapeutic appeal of these treatments is far reaching, and many new applications continue to evolve. In particular, immune modulating drugs have the potential to enhance the systemic anticancer immune effects induced by locoregional thermal ablation. The immune responses induced by ablation monotherapy are well documented, but independently they tend to be incapable of evoking a robust antitumor response. By adding immunomodulators to traditional ablative techniques, several researchers have sought to amplify the induced immune response and trigger systemic antitumor activity. This paper summarizes the work done in animal models to investigate the immune effects induced by the combination of ablative therapy and immunomodulation. Combination therapy with radiofrequency ablation, cryoablation, and microwave ablation are all reviewed, and special attention has been paid to the addition of checkpoint blockades.

Checkpoint inhibitors have demonstrated clinical impact in colorectal cancer with deficient mismatch repair and high microsatellite instability. However, the majority of patients have disease with stable microsatellites that responds poorly to immunotherapies. Combinations of checkpoint inhibitors are under investigation as a way of increasing immunogenicity and promoting a robust anti-tumor immune response. The purpose of this study is to quantify the immune responses induced by mono and dual checkpoint inhibition in a mismatch repair proficient model of colorectal cancer (CRC). Tumor growth rates were monitored over time and compared between groups. We utilized fluorescence-activated cell sorting to analyze CD8+ and CD4+ T cells after treatment with either single PD-1 inhibition or dual PD-1 and CTLA-4 inhibition. Additionally, we sought to quantify the expression of co-inhibitory surface molecules PD-1, LAG3, and TIM3. Dual checkpoint inhibition was associated with a significantly slower growth rate as compared to either mono PD-1 inhibition or control (p < 0.05). Neither monotherapy nor dual checkpoint inhibition significantly affected the tumoral infiltration of lymphocytes. After treatment with dual inhibitors, infiltrating CD8+ T cells demonstrated significantly less expression of PD-1 (1700 vs. 2545 and 2462; p < 0.05) and LAG3 (446.2 vs. 694.4 and 707; p < 0.05) along with significantly more expression of TIM3 (12,611 vs. 2961 and 4259; p < 0.05) versus the control and anti-PD-1 groups. These results suggest that dual therapy with anti-CTLA-4 and anti-PD-1 antibodies significantly inhibits growth of microsatellite stable CRC by suppressing immunosuppressive checkpoints. Upregulation of TIM3 represents a potential escape mechanism and a target for future combination immunotherapies in CRC.

Autism Spectrum Disorder (ASD) is a dreaded diagnosis. The treatment options are sparse and our knowledge of its etiology is woefully lacking. The purpose of this review is to outline a unifying pathway for the pathogenesis of Autism Spectrum Disorder and to describe how this sequence could be exploited to offer early intervention to patients at high risk of developing ASD. Specifically, we will describe how gestational insults can alter the lifelong functioning of fetal microglia. Those aberrant microglia are unable to properly fulfill their roles in cortical differentiation as well as synaptogenesis and the resulting cortical disorganization plus dendritic overgrowth may be responsible for the characteristic Autistic phenotype. This pathogenic pathway presents several opportunities for intervention. If applied early enough, it is possible that these therapies could alleviate some of the symptoms of ASD.

Thermal ablation occupies a unique position among the various modalities available to treat malignancies. Initially utilized as a minimally invasive form of palliation, ablative techniques are increasingly being recognized for their role in activating an immune response. Locally destructive, but not thoroughly extirpative, thermal ablation function to generate an in situ tumor vaccine capable of stimulating and enhancing both innate and adaptive immune responses. As monotherapy, the response engendered remains therapeutically insufficient, but newer data suggests that when used as an adjuvant or neoadjuvant, ablation may synergistically boost the anticancer immune response produced by other, sequentially acting immunotherapies. The purpose of this review is to discuss the local and systemic immunological effects induced by thermal ablation. Radio frequency, microwave, and cryoablation will all be considered in addition to focused ultrasound ablation.

Personalized medicine is revolutionizing oncologic care. Molecular and imaging “fingerprinting” of cancer through genomics, radiomics, and radiogenomics has allowed for the meticulous characterization of many forms of malignancy, including primary liver cancers. With this data, treatments are being developed that precisely target and exploit key variations in individual tumors. As these methods continue to evolve, interventional oncologists are well positioned to capitalize on the advances being made. This article will provide a concise overview of the genomic, radiomic, and radiogenomic research on hepatocellular carcinoma and intrahepatic cholangiocarcinoma, in addition to discussions on how precision medicine would relate to interventional oncology.

The reinfusion of autologous or allogeneic immune cells that have been educated and/or engineered ex vivo to respond to tumor-specific antigens is termed “adoptive cell therapy.” While adoptive cell therapy has made tremendous strides in the treatment of hematologic malignancies, its utilization for solid tumors has lagged somewhat behind. The purpose of this article is to concisely review the clinical research that has been done to investigate adoptive cell therapy as a treatment for gastrointestinal malignancies.

This review aims to investigate the current literature on genetic and genomic biomarkers of locoregional interventions on metastatic liver metastases. A brief overview on the most common cancers that metastasize to the liver and the role locoregional therapies, such as ablation, chemoembolization, and radioembolization, play in their treatment will be presented. Review of the literature on the genetic, metabolic, and other molecular biomarkers and how they relate to posttreatment survival and outcomes will be discussed. Evaluation of how the existing data can better inform decisions regarding locoregional treatments in those patients with metastatic lesions of the liver will be completed. Personalized treatment paradigms in different types of metastatic cancer present significant opportunities for improved overall clinical outcomes. Optimizing patient selection for localized treatments is vital to improving outcomes and determining which biomarkers correlate with improved efficacy presents many avenues for future research.

No abstract