Search Results (792)

Upper tract urothelial carcinoma (UTUC) accounts for approximately 5–10% of diagnosed urothelial carcinoma (UC). Due to advanced initial presentation or aggressive progression of UTUC, the majority of patients will need systematic treatment in the neo-adjuvant or adjuvant setting. The management of patients with UTUC is complicated due to the lack of published data and only limited studies addressing immunotherapy in UTUC patients are available. The perioperative scenario in localized high-risk disease is still evolving. For metastatic disease, two monoclonal antibodies targeting PD-1 (pembrolizumab and nivolumab) and three to its ligand PD-L1 (atezolizumab, avelumab and durvalumab) have obtained approval for the second-line treatment of platinum-pretreated patients. Atezolizumab and pembrolizumab are currently approved in the first-line setting for cisplatin ineligible patients, with PD-L1- positive tumors. The aim of this review was to highlight the role of immunotherapy in locally advanced and metastatic UTUC and provide the safety profile of these regimens. Full article

Background: A substantial proportion of patients with non-small cell lung cancer (NSCLC) derive limited clinical benefit from immunotherapy. Monitoring of peripheral blood immune markers (PBIMs) may emerge as a useful tool to predict treatment outcomes with immune checkpoint inhibitors (ICIs). Patients/Methods: We prospectively measured several PBIMs in a PD-L1 high (TPS ≥ 50%) NSCLC cohort of patients treated with first-line pembrolizumab monotherapy. Kinetics over the first year of treatment were assessed at baseline (T0) and at 21 days (T1), 3 months (T2), 6 months (T3) and at 1 year (T4) post-treatment initiation. Associations with clinical outcomes were explored after a 2-year follow-up period. Results: In total, 31 patients with PD-L1 high locally advanced or metastatic NSCLC were prospectively enrolled. Over the first year of treatment, levels of CRP, IL-17α, IL-6, and IL-8 were significantly decreased. Early kinetics analysis showed significant decrease in total leukocytes, neutrophils, CRP, and MIP-3α/CCL20, as well as significant transient elevation of ITAC/CXCL11, IL-1β, IL-7, and TNFα, during the first 3 months of treatment. Early percent changes (Δ% at T1 and at T2) of ‘low’ vs. ‘high’ pretreatment levels showed significant differences for LDH, ITAC/CXCL11, GM-CSF, MIP-1α/CCL3, IL-2, IL-4, IL-5, and sPD-L1. Longitudinal analysis, stratified per responders and for pre-progression fluctuations, did not reveal significant findings. Among markers with acceptable discriminative performance, higher baseline CRP, complement C4, and IL-6 levels were associated with poorer clinical outcomes. In multivariable analysis, only C4 retained independent prognostic significance; however, integration of these PBIMs into composite indices improved prognostic performance. Conclusions: In this prospective study, longitudinal monitoring of PBIMs provided descriptive insights into immune and inflammatory dynamics during pembrolizumab treatment; however, no significant associations were observed between in-treatment biomarker kinetics and clinical outcomes. In exploratory analyses, baseline CRP, complement C4, and IL-6 levels were associated with clinical outcomes, and their integration into composite indices improved prognostic performance. These findings suggest that specific baseline PBIMs may carry prognostic relevance, while the role of in-treatment monitoring remains to be further clarified in larger prospective studies. Full article

Background/Objectives: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, providing substantial survival benefits across a wide range of malignancies. However, ICI-associated renal toxicity encompasses a broad spectrum of clinical entities, ranging from nonspecific acute kidney injury to well-defined immune-mediated nephropathies with distinct pathophysiological mechanisms. Methods: We performed a large-scale pharmacovigilance study using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database to evaluate immune-mediated nephropathy associated with ICIs from January 2014 to March 2025. To improve specificity and minimize misclassification, the analysis was restricted to well-defined immune-mediated renal adverse events identified using MedDRA Preferred Terms, excluding nonspecific acute kidney injury. Disproportionality analysis was conducted using reporting odds ratios (RORs) with 95% confidence intervals (CIs) to assess associations between individual ICIs, treatment regimens, and nephropathy reporting. Results: Among 203,652 ICI-related adverse event reports (irAEs), 2361 (1.12%) involved immune-mediated nephropathy. Compared with other irAEs (non-nephropathy), immune-mediated nephropathy was more frequently reported in patients aged ≥ 65 years and in those with lung and genitourinary malignancies. Tubulointerstitial nephritis was the predominant subtype. Higher reporting signals were observed with cemiplimab and pembrolizumab, whereas durvalumab and atezolizumab demonstrated lower reporting signals. Combination regimens involving PD-1 and CTLA-4 inhibitors were associated with higher reporting frequencies compared with monotherapy. Conclusions: This real-world pharmacovigilance analysis identifies clinically relevant differences in immune-mediated nephropathy reporting across ICI classes and treatment strategies. PD-1 inhibitors and PD-1/CTLA-4 combination regimens were associated with higher reporting signals, suggesting potential variation in renal safety profiles. These findings should be interpreted cautiously, given the inherent limitations of spontaneous reporting systems, but they provide hypothesis-generating evidence to support future prospective studies with detailed clinical and histopathological correlation. Full article

Fanconi anemia (FA) is a rare inherited disorder associated with impaired DNA repair, characterized by congenital anomalies, bone marrow failure, and a significantly increased risk of developing malignancies, particularly squamous cell carcinoma (SCC) of the head and neck. Treatment options for advanced SCC in FA are limited due to hypersensitivity to DNA-damaging agents. This article presents a unique case of SCC that developed in a 17-year-old patient with FA caused by a homozygous mutation in the FANCA gene. At the age of 10, he received a bone marrow transplant from a compatible related donor. Conditioning therapy included busulfan, thymoglobulin, and fludarabine, while graft-versus-host disease (GvHD) prophylaxis was administered with rituximab, methotrexate, and cyclosporine A. Nevertheless, he developed chronic cutaneous GVHD, which was treated for four years with ruxolitinib and tacrolimus, achieving only partial control. During this period, locally advanced cutaneous SCC (T3N0M0, stage III) manifested on the face. Surgery, radiation therapy, and immunotherapy with pembrolizumab led only to an initial partial response. This first pediatric case of immunotherapy for SCC in FA highlights the challenges of treating this rare patient group. Nevertheless, combining radiation therapy with immunotherapy may represent a possible option for disease control. Full article

Triple-negative breast cancer (TNBC) represents a biologically aggressive subtype with limited therapeutic targets; however, tumor-infiltrating lymphocytes (TILs) have emerged as the most robust immune biomarker with compelling prognostic and predictive significance. This comprehensive review synthesizes current evidence on TIL assessment methodology; the immunobiological landscape of TNBC, including regulatory T cell populations and PD-L1 correlations; gene expression underpinnings of the tumor immune microenvironment; and systematic evidence from meta-analyses and clinical trials. Meta-analytic estimates demonstrate that high TIL levels are associated with improved overall survival (HR 0.58, 95% CI 0.48–0.71) and disease-free survival (HR 0.66, 95% CI 0.57–0.76), with each 10% TIL increment conferring incremental benefit. High TILs predict superior pathologic complete response to neoadjuvant chemotherapy (OR 2.14, 95% CI 1.43–3.19), with lymphocyte-predominant breast cancer achieving pCR rates exceeding 80% with pembrolizumab-based chemoimmunotherapy. Future directions include prospective TIL-guided treatment trials, artificial intelligence-enabled standardization, and emerging adoptive TIL cellular therapies for metastatic disease. Full article

Background: Chemoimmunotherapy has improved survival compared with chemotherapy alone in phase III trials of advanced oesophago-gastric (OG) cancers; however, real-world UK data under National Institute for Health and Care Excellence (NICE) eligibility criteria remain limited. This study evaluated the effectiveness and safety of first-line pembrolizumab- or nivolumab-based chemoimmunotherapy in routine clinical practice. Methods: We conducted a retrospective, multi-centre cohort study of patients with unresectable or metastatic oesophageal, gastro-oesophageal junction, or gastric cancers treated with first-line chemoimmunotherapy at two UK tertiary centres between April 2021 and July 2024. Clinical, laboratory, radiological, and toxicity data were collected. Radiological outcomes were based on retrospective review of reports issued by consultant radiologists during routine clinical care. Overall survival (OS) and progression-free survival (PFS) were analysed using the Kaplan–Meier method, with exploratory analyses of prognostic factors. Results: Seventy-six patients were included (59.2% ≥ 65 years; 81.6% adenocarcinoma; 71.1% metastatic). At a median follow-up of 11 months, 46 deaths had occurred. Median OS was 16.0 months (95% CI: 11.0–20.9), and median PFS was 8.0 months (95% CI: 6.8–9.2). Disease control occurred in 80.3% of patients and was associated with improved OS compared with progressive disease (17.0 vs. 4.0 months; p < 0.001). Survival outcomes did not differ significantly by tumour site, histology, or immunotherapy agent. Immunotherapy-related adverse events occurred in 31 patients (40.8%), with grade ≥ 3 toxicities in 13.2% and two treatment-related deaths. Exploratory analyses suggested potential associations between survival and baseline lymphocyte count and neutrophil–lymphocyte ratio, although these did not reach statistical significance. Conclusions: In this real-world UK multi-centre cohort, first-line chemoimmunotherapy demonstrated survival outcomes comparable to pivotal clinical trials, with manageable toxicity. These findings support the use of chemoimmunotherapy in routine practice. Prospective collaborative studies incorporating robust biomarker evaluation are warranted to optimise patient selection and better define predictors of response and toxicity. Full article

Combined immune checkpoint inhibition (ICI) and multitargeted tyrosine kinase inhibition (TKI) improve outcomes in advanced melanoma, especially in heavily pretreated patients, but introduce complex, overlapping toxicities. Although immune-related adverse events and TKI-specific toxicities are well characterized individually, their concurrent presentation is uncommon and can obscure diagnosis. Capillary leak syndrome (CLS), a rare but potentially life-threatening complication of ICIs, further complicates recognition due to nonspecific features and variable onset. A 43-year-old woman with metastatic BRAF wild-type melanoma, in complete metabolic response on lenvatinib and pembrolizumab, presented with generalized edema, hypotension, thrombocytopenia, and marked erythroblastosis. Extensive evaluation, including bone marrow analysis, excluded malignancy, infection, and autoimmune disease, but revealed multilineage dysplasia with pronounced erythroid stress. Imaging confirmed sustained remission with pleural effusions and ascites. Dual toxicity was suspected: lenvatinib-related hematologic toxicity and pembrolizumab-associated CLS. Both agents were discontinued, and corticosteroids followed by IVIG for steroid-refractory edema led to gradual recovery. This case underscores the diagnostic challenge of overlapping ICI–TKI toxicities. Mechanistically, VEGF pathway inhibition may disrupt marrow endothelial integrity and hematopoietic homeostasis, promoting cytopenias and erythroid precursor release, while immune activation drives cytokine-mediated endothelial dysfunction and vascular hyperpermeability. Early recognition and prompt immunomodulatory management are critical to improving outcomes. Full article

Background: Pembrolizumab combined with pemetrexed–platinum chemotherapy is the standard first-line treatment for patients with metastatic non-squamous non-small-cell lung cancer (NSCLC) and a PD-L1 tumor proportion score (TPS) of 1–49%. Real-world data on treatment outcomes and the prognostic relevance of immune-related adverse events (irAEs) in this population remain limited, particularly in Eastern Europe. Methods: We conducted a retrospective, single-center real-world study including patients with metastatic non-squamous NSCLC and PD-L1 TPS of 1–49% treated with first-line pembrolizumab plus pemetrexed–platinum chemotherapy between June 2024 and May 2025. Progression-free survival (PFS) was estimated using the Kaplan–Meier method. Cox proportional hazards models were used to evaluate factors associated with PFS, including baseline clinical characteristics and organ-specific irAEs graded according to CTCAE v5.0. Results: A total of 107 patients were included. Median PFS for the entire cohort was 7.03 months (95% CI, 4.81–9.26). Immune-related adverse events occurred in 52 patients (48.6%), with thyroid (21.5%) and skin (13.1%) irAEs being the most frequent. The majority of irAEs were grade 1–2, while grade 3–4 events were rare (4.7%) and limited to hepatic toxicity and pneumonitis, all leading to treatment discontinuation. In multivariate analysis, ECOG performance status 2 was independently associated with inferior PFS (HR 3.09, 95% CI 1.74–5.48; p < 0.001). Conversely, the occurrence of thyroid irAEs (HR 0.36, 95% CI 0.17–0.78; p = 0.009) and skin irAEs (HR 0.28, 95% CI 0.10–0.79; p = 0.016) was independently associated with prolonged PFS, whereas pulmonary, hepatic, and gastrointestinal irAEs were not. Conclusions: In this real-world cohort of patients with metastatic non-squamous NSCLC treated with first-line pembrolizumab–chemotherapy, clinical outcomes were consistent with prior real-world experience. These findings suggest that low-grade, manageable immune toxicities may serve as pragmatic on-treatment markers of benefit. However, given the retrospective design, limited sample size, and the absence of time-dependent analyses, these associations should be interpreted with caution and considered hypothesis-generating rather than causal. Full article

The treatment of locally advanced cervical cancer is based on concomitant cisplatin-based chemoradiotherapy followed by brachytherapy. The quality of this treatment is essential to optimize results. In particular, intensity-modulated radiotherapy followed by image-guided brachytherapy achieves 90% local control regardless of the stage of the disease. More recently, several randomized trials have changed the management of these tumors: The INTERLACE trial evaluated the benefits of neoadjuvant chemotherapy with carboplatin and paclitaxel and demonstrated a survival benefit for this approach. This trial has been the subject of considerable criticism. The KEYNOTE A.18 trial evaluated the addition of pembrolizumab to standard treatment: an improvement in overall survival was demonstrated for patients with stage III-IV disease (FIGO 2014 classification). The CALLA trial, which evaluated the addition of durvalumab, was negative. This review summarizes the biological rationale for this immunotherapy, its results, and the quality criteria for chemoradiotherapy. It describes the various trials in detail, puts their results into context, and discusses the relevance of this new treatment based on the patients’ baseline characteristics. Based on this critical analysis, patients with stage III-IVA cervical cancer (FIGO 2014 classification) should receive, in addition to standard chemoradiotherapy, concomitant treatment with pembrolizumab followed by two years of maintenance therapy. Full article

Background: Guillain–Barré syndrome (GBS) is an autoimmune peripheral neuropathy that can lead to paralysis and respiratory failure. In addition to infections, several drugs have been suggested as potential triggers of GBS. This study investigated drug-associated GBS using a spontaneous adverse event reporting database through disproportionality analysis for signal detection and time-to-onset analysis. Methods: The Japanese Adverse Drug Event Report (JADER) database was analyzed to assess more than 4000 drugs for potential associations with GBS. Signal detection was performed using reporting odds ratios, Fisher’s exact test, and total report counts. For vaccines and immune checkpoint inhibitors, time-to-onset patterns were further evaluated using Weibull distribution analysis. Results: Disproportionality signals suggesting potential associations with GBS were identified for 45 drugs, including vaccines, immune checkpoint inhibitors, tumor necrosis factor-α inhibitors, other anticancer drugs, antifungal agents, and interferons. Reports following vaccination were most frequently observed within 1–3 weeks after administration of coronavirus disease 2019 (COVID-19), influenza, and pneumococcal vaccines, and within 1–3 months after human papillomavirus 2-valent vaccination, with a gradual decrease thereafter. Reports following immune checkpoint inhibitor use were most frequently observed 1–3 months after nivolumab, ipilimumab, and pembrolizumab administration, whereas atezolizumab showed a peak in reporting within 1–3 weeks. In contrast to vaccine-related reports, no clear temporal trend in reporting was observed. Conclusions: Drugs that modulate immune function, including vaccines and immune checkpoint inhibitors, may be associated with reported GBS events. Vaccine-related reports showed an early concentration in time to onset, whereas immune checkpoint inhibitor-related reports did not demonstrate a clear temporal pattern. These findings should be interpreted as hypothesis-generating and warrant further investigation. Full article

Cutaneous melanoma is the most lethal form of skin cancer because of its aggressiveness, rapid metastasis, and high therapeutic resistance. The 2018 World Health Organization (WHO) classification emphasized that melanoma comprises distinct subtypes defined by cumulative sun damage, site of origin, and molecular characteristics, which explain differences in mutational burden, immunogenicity, and treatment response. Immunotherapy with anti-PD-1 therapy such as nivolumab and pembrolizumab changed the therapeutic landscape by restoring CD8+ T-cell activity and improving survival. Still, many patients show primary or acquired resistance influenced by low PD-L1 expression, loss of antigen presentation, tumor metabolic plasticity, and an immunosuppressive microenvironment. Mitochondria are central to this process. They regulate ATP generation through oxidative phosphorylation (OXPHOS), redox control, apoptosis, and the metabolic programming needed for T-cell activation. In the tumor microenvironment (TME), hypoxia, nutrient restriction, and PD-1 signaling reduce mitochondrial biogenesis, increase fission and reactive oxygen species (ROS) accumulation, and lead to exhaustion and impaired effector function. Moreover, tumor cells outcompete immune cells for key nutrients such as glucose and glutamine, while increased lactate production and extracellular acidosis further suppress mitochondrial respiration in T cells. Strategies to overcome resistance include restoring oxidative metabolism, activating PGC-1α, supplying metabolic substrates, and combining checkpoint blockade with inhibitors of glycolysis or glutaminolysis to enhance the immune response. Full article

Background: Atypical teratoid/rhabdoid tumors (AT/RT) are rare, highly aggressive pediatric central nervous system (CNS) malignancies. AT/RT of the lateral ventricle is an exceptionally rare subgroup, with only 11 reported cases. SMARCB1 inactivation is the primary molecular feature of AT/RT. Current consensus is to classify AT/RT based on methylation and molecular profiles into the following subgroups: AT/RT-TYR, AT/RT-SHH, AT/RT-MYC, and a potentially distinct SMARCA4-deficient subtype. AT/RT-MYC exhibits high levels of CD8⁺ tumor-infiltrating lymphocytes, indicating immunogenic potential. Case presentation: We report three pediatric cases presenting with intracranial hypertension and seizures. Diagnosis was confirmed via histopathology and molecular profiling. Interventions included gross total resection, chemotherapy, radiotherapy, and combined immune checkpoint inhibitors (pembrolizumab and ipilimumab). Outcomes varied from rapid progression to 3-year recurrence-free survival. A cohort of 14 pediatric patients with lateral ventricle AT/RT, comprising 3 institutional cases and 11 cases identified from the PubMed database, was evaluated through a narrative synthesis. Conclusions: These advancements highlight the crucial role of molecular subtyping in tailoring personalized treatments, including epigenetic modifiers and immune-based regimens. However, clinical validation is essential to establish standardized protocols. Integrating genomic, epigenetic, and immune microenvironment profiling may enhance risk assessment and treatment precision, ultimately improving survival and quality of life in pediatric patients. Full article

Background: This study aimed to evaluate the effectiveness and safety of first-line pembrolizumab monotherapy in patients with advanced non-small cell lung cancer (NSCLC) in real-world clinical practice in Vietnam. Methods: We performed a multicenter retrospective cohort study of patients with locally advanced or metastatic NSCLC who received first-line pembrolizumab monotherapy in Vietnam between January 2018 and August 2024. The primary endpoints were progression-free survival (PFS), overall survival (OS), and safety profile. Results: A total of 73 patients were included, with a median age of 69 years (range, 47–92). Most patients had good performance status (ECOG PS 0–1, 75.3%) and high PD-L1 expression (TPS ≥ 50%, 86.3%). The overall response rate was 60.3%, and the disease control rate was 79.5%. Median PFS was 11.3 months (95% CI, 6.9–15.8), and median OS was 25.4 months (95% CI, 20.8–30.0). Multivariate analysis identified never-smoking status (HR 3.14, 95% CI 1.16–8.50; p = 0.024), squamous histology (HR 4.09, 95% CI 1.18–14.17; p = 0.026), and low PD-L1 expression (TPS 1–49%) (HR 3.67, 95% CI 1.14–11.78; p = 0.029) as independent predictors of inferior overall survival. Immune-related adverse events, including pneumonitis, hepatitis, nephritis, fever, skin reactions, and myositis, were mostly mild and manageable, with grade 3 toxicity occurring in only 4.2% of patients. Better survival was observed in patients with high PD-L1 expression and non-squamous histology. However, the association with non-squamous histology should be interpreted with caution due to the very small number of squamous cases. Conclusions: First-line pembrolizumab monotherapy demonstrated favorable effectiveness and acceptable safety in patients with advanced NSCLC in real-world clinical practice in Vietnam. Clinical outcomes were particularly favorable in patients with high PD-L1 expression, non-squamous histology, and a history of smoking. Nevertheless, the survival benefit associated with non-squamous histology should be interpreted cautiously, given the limited number of patients with squamous histology. These findings support the use of pembrolizumab monotherapy in selected patient populations within resource-limited settings. Full article

The management of urothelial carcinoma (UC) is undergoing a paradigm shift from static anatomical staging to molecularly guided dynamic approaches that integrate time as a critical therapeutic variable. This evolution is driven by liquid biopsies, particularly circulating tumor DNA, which allow real-time tumor interrogation. We conducted this expert review to synthesize landmark evidence, enabling technologies, and implementation challenges in dynamic precision oncology for UC. In this non-systematic narrative review, we searched PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library for articles published between January 2015 and February 2026. Studies were selected based on their relevance to dynamic precision oncology, clinical actionability, and translational implementation, prioritizing landmark randomized controlled trials providing level 1–2 evidence, large prospective cohorts, and key translational studies. Enfortumab vedotin plus pembrolizumab established the new first-line standard for metastatic UC, achieving a median overall survival of 33.8 months versus 15.9 months (hazard ratio [HR] 0.51, 95% confidence interval 0.43–0.61). Circulating tumor DNA demonstrates robust prognostic value for molecular residual disease (MRD) detection (Level 2a evidence), stratifying recurrence risk with hazard ratios of approximately 4.5. Critically, the IMvigor011 trial has now provided Level 1b evidence that ctDNA-guided adjuvant atezolizumab improves both disease-free survival (DFS) (HR 0.64, p = 0.0047) and OS (HR 0.59, p = 0.0131) in ctDNA(+) patients, while validating treatment de-escalation in ctDNA(−) patients (1-year DFS 95%). Erdafitinib in patients harboring FGFR2/3 alterations (HR 0.64) confirms the value of genomic profiling. Major limitations include the inherent selection bias of this non-systematic approach, substantial platform heterogeneity, and lack of standardization. In conclusion, dynamic precision oncology has transformed UC management, with the IMvigor011 trial establishing ctDNA-guided MRD status as the first phase 3-validated predictive biomarker framework for adjuvant therapy selection in a solid tumor. Implementation requires adherence to established standardization frameworks, cross-platform and cross-agent validations, and tiered implementation strategies to ensure equitable access across diverse resource settings. Full article

Oncolytic viruses represent a paradigm-shifting approach to cancer immunotherapy, functioning as in situ vaccines that convert immunologically “cold” tumors into “hot” tumors through induction of immunogenic cell death (ICD). Despite the clinical success of checkpoint inhibitors targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), many patients exhibit primary or acquired resistance due to insufficient tumor immunogenicity and exclusion of tumor-infiltrating lymphocytes. Oncolytic viruses address this limitation by selectively replicating in tumor cells, inducing robust ICD characterized by four cardinal hallmarks: calreticulin exposure, ATP secretion, HMGB1 release, and type I interferon production. This review systematically examines the molecular mechanisms underlying virus-induced ICD, compares DNA virus platforms (Vaccinia, HSV-1, Adenovirus) with RNA virus platforms (Coxsackieviruses A21, A11, and B3), and analyzes clinical trial data demonstrating synergistic efficacy when combined with checkpoint inhibitors. Notably, RNA viruses generate higher type I interferon responses compared to DNA viruses, correlating with superior clinical outcomes. Coxsackievirus A21 combined with pembrolizumab achieved a 47% objective response rate in melanoma in the CAPRA trial, representing notable efficacy exceeding either monotherapy. Coxsackievirus A11 demonstrates exceptional selectivity for thoracic cancers through ICAM-1-dependent receptor tropism and potent immunogenic cell death induction. Japanese researchers have pioneered microRNA-targeted Coxsackievirus B3, achieving cardiac safety attenuation while preserving complete oncolytic potency and ICD-inducing capacity. This comprehensive analysis synthesizes molecular mechanisms, platform comparisons, clinical efficacy data, and translational challenges to guide future development of oncolytic virotherapy as a cornerstone of cancer immunotherapy. Full article