Cancer immunotherapy and the emergence of immune checkpoint inhibitors have markedly changed the treatment paradigm for many cancers. They function to disrupt cancer cell evasion of the immune response and activate sustained anti-tumor immunity. Oncolytic viruses have also emerged as an additional therapeutic agent for cancer treatment. These viruses are designed to target and kill tumor cells while leaving the normal cells unharmed. As part of this process, oncolytic virus infection stimulates anti-cancer immune responses that augment the efficacy of checkpoint inhibition. These viruses have the capability of transforming a "cold" tumor microenvironment with few immune effector cells into a "hot" environment with increased immune cell and cytokine infiltration. For this reason, there are multiple ongoing clinical trials that combine oncolytic virotherapy and immune checkpoint inhibitors. This review will detail the key oncolytic viruses in preclinical and clinical studies and highlight the results of their testing with checkpoint inhibitors.

Advances in the understanding of cancer immunotherapy and the development of multiple checkpoint inhibitors have dramatically changed the current landscape of cancer treatment. Recent large‐scale phase III trials (e.g. PHOCUS, OPTiM) are establishing use of oncolytic viruses as another tool in the cancer therapeutics armamentarium. These viruses do not simply lyse cells to achieve their cancer‐killing effects, but also cause dramatic changes in the tumor immune microenvironment. This review will highlight the major vector platforms that are currently in development (including adenoviruses, reoviruses, vaccinia viruses, herpesviruses, and coxsackieviruses) and how they are combined with checkpoint inhibitors. These vectors employ a variety of engineered capsid modifications to enhance infectivity, genome deletions or promoter elements to confer selective replication, and encode a variety of transgenes to enhance anti‐tumor or immunogenic effects. Pre‐clinical and clinical data have shown that oncolytic vectors can induce anti‐tumor immunity and markedly increase immune cell infiltration (including cytotoxic CD8⁺ T cells) into the local tumor microenvironment. This “priming” by the viral infection can change a ‘cold’ tumor microenvironment into a ‘hot’ one with the influx of a multitude of immune cells and cytokines. This alteration sets the stage for subsequent checkpoint inhibitor delivery, as they are most effective in an environment with a large lymphocytic infiltrate. There are multiple ongoing clinical trials that are currently combining oncolytic viruses with checkpoint inhibitors (e.g. CAPTIVE, CAPRA, and Masterkey‐265), and the initial results are encouraging. It is clear that oncolytic viruses and checkpoint inhibitors will continue to evolve together as a combination therapy for multiple types of cancers.

Intrahepatic cholangiocarcinomas (ICCs) are the second most common type of primary liver cancer.¹ Approximately 10% of all cholangiocarcinomas are intrahepatic, amounting to 2000 to 3000 cases each year in the United States with an increasing incidence worldwide.^2,3 Intrahepatic cholangiocarcinomas are resistant to chemotherapy and radiotherapy, and surgical resection is considered to be the mainstay of therapy, providing the only chance of cure. However, most patients have advanced disease at diagnosis and are not candidates for surgery. Resectability is defined by the ability to completely resect ICC while leaving an adequate liver remnant. Current consensus considers noncontiguous extrahepatic disease, multiple bilobar or multicentric tumors, or lymph node metastases beyond the primary echelon as contraindications to resection.⁴ The role of surgical resection for large or multifocal ICCs or those invading adjacent organs by direct extension remains unclear. The decision to pursue resection is complex because of unclear oncologic benefit and substantial rates of operative morbidity and mortality.

Oncolytic viruses are a new class of therapeutics which are largely in the experimental stage, with just one virus approved by the FDA thus far. While the concept of oncolytic virotherapy is not new, advancements in the fields of molecular biology and virology have renewed the interest in using viruses as oncolytic agents. Backed by robust preclinical data, many oncolytic viruses have entered clinical trials. Oncolytic viruses that have completed some levels of clinical trials or are currently undergoing clinical trials are mostly genetically engineered viruses, with the exception of some RNA viruses. Reolysin, an unmodified RNA virus is clinically the most advanced oncolytic RNA virus that has completed different phases of clinical trials. Other oncolytic viruses that have been studied in clinical trials are mostly DNA viruses that belong to one of the three families: herpesviridae, poxviridae or adenoviridae. In this review work we discuss recent clinical studies with oncolytic viruses, especially herpesvirus, poxvirus, adenovirus and reovirus. In summary, the oncolytic viruses tested so far are well tolerated, even in immune-suppressed patients. For most oncolytic viruses, mild and acceptable toxicities are seen at the currently defined highest feasible doses. However, anti-tumor efficacies of oncolytic viruses have been modest, especially when used as monotherapy. Therefore, the potency of oncolytic viruses needs to be enhanced for more oncolytic viruses to hit the clinic. Aiming to achieve higher therapeutic benefits, oncolytic viruses are currently being studied in combination with other therapies. Here we discuss the currently available clinical data on oncolytic viruses, either as monotherapy or in combination with other treatments.

Selected studies have reported improved outcomes in laparoscopic compared with open distal pancreatic resection. Concerns regarding failure to achieve proper oncological resection and compromised long-term outcomes remain. This study investigated whether postoperative outcomes and long-term survival after laparoscopic distal pancreatectomy are comparable to those after an open procedure. This retrospective case–control study included patients who underwent distal pancreatectomy for resectable pancreatic adenocarcinoma between 2010 and 2013, identified from the National Cancer Database. Propensity score nearest-neighbour 1 : 1 matching was performed between patients undergoing laparoscopic or open distal pancreatectomy based on all relevant co-variables. The primary outcome was overall survival. Of 1947 eligible patients, 605 (31·1 per cent) underwent laparoscopic distal pancreatectomy. After propensity score matching, two well balanced groups of 563 patients each were analysed. There was no difference in overall survival at 3 years after laparoscopic versus open distal pancreatectomy (41·6 versus 36·0 per cent; hazard ratio 0·93, 95 per cent c.i. 0·77 to 1·12; P = 0·457). The overall conversion rate was 27·3 per cent (165 of 605). Patients who underwent laparoscopic distal pancreatectomy had outcomes comparable to those of patients who had an open procedure with regard to median time to chemotherapy (50 versus 50 days; P = 0·342), median number of nodes examined (12 versus 12; P = 0·759); 30-day mortality (1·2 versus 0·9 per cent; P = 0·562); 90-day mortality (2·8 versus 3·7 per cent; P = 0·403), 30-day readmission rate (9·6 versus 9·2 per cent; P = 0·838) and positive margin rate (14·9 versus 18·5 per cent; P = 0·110). However, median duration of hospital stay was shorter in the laparoscopic group (6 versus 7 days; P < 0·001). Laparoscopic distal pancreatectomy is an acceptable alternative to open distal pancreatectomy with no detriment to survival.