A review of ultrasound-mediated checkpoint inhibitor immunotherapy

Over the past decade, immunotherapy has emerged as a major modality in cancer medicine. However, despite its unprecedented success, immunotherapy currently benefits only a subgroup of patients, may induce responses of limited duration and is associated with potentially treatment-limiting side effects. In addition, responses to immunotherapeutics are sometimes diminished by the emergence of a complex array of resistance mechanisms. The efficacy of immunotherapy depends on dynamic interactions between tumour cells and the immune landscape in the tumour microenvironment. Ultrasound, especially in conjunction with cavitation-promoting agents such as microbubbles, can assist in the uptake and/or local release of immunotherapeutic agents at specific target sites, thereby increasing treatment efficacy and reducing systemic toxicity. There is also increasing evidence that ultrasound and/or cavitation may themselves directly stimulate a beneficial immune response. In this review, we summarize the latest developments in the use of ultrasound and cavitation agents to promote checkpoint inhibitor immunotherapy

Comprehensive Treatment Algorithms of the Swiss Peritoneal Cancer Group for Peritoneal Cancer of Gastrointestinal Origin

Peritoneal cancer (PC) is a dire finding, yet in selected patients, long-term survival is possible. Complete cytoreductive surgery (CRS) together with combination immunochemotherapy is essential to achieve cure. Hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC) are increasingly added to the multimodal treatment. The Swiss Peritoneal Cancer Group (SPCG) is an interdisciplinary group of expert clinicians. It has developed comprehensive treatment algorithms for patients with PC from pseudomyxoma peritonei, peritoneal mesothelioma, gastric, and colorectal origin. They include multimodal neoadjuvant treatment, surgical resection, and palliative care. The indication for and results of CRS HIPEC and PIPAC are discussed in light of the current literature. Institutional volume and clinical expertise required to achieve best outcomes are underlined, while inclusion of patients considered for CRS HIPEC and PIPAC in a clinical registry is strongly advised. The present recommendations are in line with current international guidelines and provide the first comprehensive treatment proposal for patients with PC including intraperitoneal chemotherapy. The SPCG comprehensive treatment algorithms provide evidence-based guidance for the multimodal care of patients with PC of gastrointestinal origin that were endorsed by all Swiss clinicians routinely involved in the multimodal care of these challenging patients

LIN28B Underlies the Pathogenesis of a Subclass of Ewing Sarcoma

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A Phase Ib Study of the Combination of Personalized Autologous Dendritic Cell Vaccine, Aspirin, and Standard of Care Adjuvant Chemotherapy Followed by Nivolumab for Resected Pancreatic Adenocarcinoma—A Proof of Antigen Discovery Feasibility in Three Patients

Despite the promising therapeutic effects of immune checkpoint blockade (ICB), most patients with solid tumors treated with anti-PD-1/PD-L1 monotherapy do not achieve objective responses, with most tumor regressions being partial rather than complete. It is hypothesized that the absence of pre-existing antitumor immunity and/or the presence of additional tumor immune suppressive factors at the tumor microenvironment are responsible for such therapeutic failures. It is therefore clear that in order to fully exploit the potential of PD-1 blockade therapy, antitumor immune response should be amplified, while tumor immune suppression should be further attenuated. Cancer vaccines may prime patients for treatments with ICB by inducing effective anti-tumor immunity, especially in patients lacking tumor-infiltrating T-cells. These "non-inflamed" non-permissive tumors that are resistant to ICB could be rendered sensitive and transformed into "inflamed" tumor by vaccination. In this article we describe a clinical study where we use pancreatic cancer as a model, and we hypothesize that effective vaccination in pancreatic cancer patients, along with interventions that can reprogram important immunosuppressive factors in the tumor microenvironment, can enhance tumor immune recognition, thus enhancing response to PD-1/PD-L1 blockade. We incorporate into the schedule of standard of care (SOC) chemotherapy adjuvant setting a vaccine platform comprised of autologous dendritic cells loaded with personalized neoantigen peptides (PEP-DC) identified through our own proteo-genomics antigen discovery pipeline. Furthermore, we add nivolumab, an antibody against PD-1, to boost and maintain the vaccine's effect. We also demonstrate the feasibility of identifying personalized neoantigens in three pancreatic ductal adenocarcinoma (PDAC) patients, and we describe their optimal incorporation into long peptides for manufacturing into vaccine products. We finally discuss the advantages as well as the scientific and logistic challenges of such an exploratory vaccine clinical trial, and we highlight its novelty

Thrombocytose: facteur pronostique dans le cancer ovarien de type séreux de stade III et IV.

Introduction Le cancer ovarien est la 4eme cause de mortalité chez les femmes. Il demeure malheureusement trop souvent diagnostiqué à un stade avancé (70% des cas aux stades III ou IV) et le pronostic reste sombre malgré les progrès de la chimiothérapie et des thérapies ciblées. La thrombocytose (> 350 x 109 / L, N=150-350 * 109 / L) est un facteur pronostique défavorable dans de nombreux types de cancer. Nous avons étudié si la présence d'une thrombocytose au diagnostic chez les femmes atteintes d'un cancer ovarien de type séreux de stade III et IV était un possible facteur pronostique. Méthodologie : Nous avons réalisé une analyse rétrospective de 91 patientes diagnostiquées d'un cancer de l'ovaire de type séreux de stade III et IV traitées au CHUV entre 2002 et 2012. Nous avons comparé la survie globale et la survie sans progression chez des patientes avec des taux de plaquettes normaux à celle des patientes atteintes de thrombocytose. Résultats : Dans notre étude, l'âge moyen des patientes était de 66 ans. Sur les 91 patientes, 52 (57,1%) présentaient un taux de plaquettes normal (médiane : 273 x 109/ L) au moment du diagnostic et 39 patientes (42,9%) avaient une thrombocytose (médiane: 463 x 109/ L). Parmi les patientes avec une numération plaquettaire normale, 24 d'entre elles sont décédées avec une médiane de survie de 43 mois. Dans le groupe avec thrombocytose au diagnostic, 24 patientes sont décédées avec une médiane de survie de 23 mois. La différence de survie globale et de survie sans progression entre les deux groupes est statistiquement significative, respectivement de p= 0,02 et de p = 0,007. Conclusion : Dans cette analyse rétrospective de patientes atteintes de cancer ovarien de type séreux de stade III et IV, une thrombocytose au moment du diagnostic semble avoir une valeur pronostique sur la survie globale et la survie sans progression

Organoids: A New Chapter in Sarcoma Diagnosis and Treatment

Sarcomas are malignant tumors of mesenchymal origin that can occur at any age. The rarity of these tumors in combination with the vast number of histological subtypes render the study of sarcomas challenging. Organoids represent complex three-dimensional cell culture systems, deriving from stem cells and preserving the capacity to differentiate into the cell types of their tissue of origin. The aim of the present review is to study the current status of patient-derived organoids, as well as their potential to model tumorigenesis and perform drug screenings for sarcomas. In order to identify relevant studies, a literature review was conducted and we were able to identify 16 studies published between 2019 and 2022. The current manuscript represents the first comprehensive review of the literature focusing on the use of organoids for disease modelling and drug sensitivity testing in diverse sarcoma subtypes

Immunotherapy for Esophageal Cancer: State-of-the Art in 2021

Simple Summary The aim of this review was to describe the rationale for immunotherapy in different stages of esophageal cancer (EC) treatment, with a particular accent on curative intent treatment of locally advanced disease for the two predominant histological types (adenocarcinoma and squamous cell cancer). In addition to the already existing literature on immunotherapy for advanced and metastatic stages of EC, the current study provides a comprehensive review of the leading ongoing trials in 2021 with a focus on earlier stages of treatment in neo adjuvant and adjuvant settings. The management of esophageal cancer (EC) has experienced manifold changes during the last decades. Centralization of EC treatment has been introduced in many countries, subsequently allowing the development of specialized high-volume centers. Minimal invasive surgery has replaced open surgery in many centers, whereas more potent systemic treatments have been introduced in clinical practice. Newer chemotherapy regimens increase long-term survival. Nevertheless, the overall survival of EC patients remains dismal for advanced tumor stages. In this direction, a wide range of targeted biologic agents (immunotherapy) is currently under assessment. Anti- Human Epidermal Growth Factor Receptor-2 (HER-2) monoclonal antibodies are used in HER2 (+) tumors, predominantly well-differentiated adenocarcinomas, and are currently assessed in the neoadjuvant setting (TRAP, INNOVATION trials). Immune checkpoint inhibitors Nivolumab (ATTRACTION-03) and pembrolizumab (KEYNOTE-181), have demonstrated a survival benefit compared with conventional chemotherapy in heavily pre-treated progressive disease. More recently, CheckMate-577 showed very promising results for nivolumab in a curative adjuvant setting, improving disease-free survival mainly for esophageal squamous cell carcinoma. Several ongoing trials are investigating novel targeted agents in the preoperative setting of locally advanced EC. In addition, other immunomodulatory approaches such as peptide vaccines and tumor infiltrating lymphocytes (TILs) are currently under development and should be increasingly integrated into clinical practice

Clear cell sarcoma: state-of-the art and perspectives

Introduction: Clear cell sarcoma (CCS) is an ultra-rare soft tissue sarcoma (STS) with a poor prognosis due to propensity to metastasize and its low chemosensitivity. The standard treatment of localized CCS consists of wide surgical excision with or without additive radiotherapy. On the other hand, unresectable CCS is generally treated with conventional systemic therapies available for treatment of STS despite the weak scientific evidence to support its use. Areas covered: In this review, we discuss the clinicopathologic characteristics of CSS, as well as the current treatment landscape and future therapeutic approaches. Expert opinion: The current treatment strategy of advanced CCSs, based on STSs regimens, shows a lack of effective options. Combination therapies, in particular the association of immunotherapy and TKIs, represent a promising approach. Translational studies are needed in order to decipher the regulatory mechanisms involved in the oncogenesis of this ultra-rare sarcoma and identify potential molecular targets