Abscopal Effects in Metastatic Cancer: Is a Predictive Approach Possible to Improve Individual Outcomes?

Patients with metastatic cancers often require radiotherapy (RT) as a palliative therapy for cancer pain. RT can, however, also induce systemic antitumor effects outside of the irradiated field (abscopal effects) in various cancer entities. The occurrence of the abscopal effect is associated with a specific immunological activation in response to RT-induced cell death, which is mainly seen under concomitant immune checkpoint blockade. Even if the number of reported apscopal effects has increased since the introduction of immune checkpoint inhibition, its occurrence is still considered rare and unpredictable. The cases reported so far may nevertheless allow for identifying first biomarkers and clinical patterns. We here review biomarkers that may be helpful to predict the occurrence of abscopal effects and hence to optimize therapy for patients with metastatic cancers.

COVID-19: From viral infection to pulmonary failure

SARS-CoV-2 is a virus which promoted a worldwide pandemic outbreak in 2020. The virus is highly infectious and is able to contaminate a lot of people in a short time period. The disease promoted by the virus, named COVID-19, can cause different symptoms such as fever, cough, muscle pain, headache, prostration, diarrhea, neurological complications, dermic manifestations, pulmonary impairment, dyspnea, coagulopathies, organ failure, and death. Here, we show how the infection occurs and the major characteristics observed in the lungs of patients with COVID-19. In addition, we explored the immunological activation in this environment by the virus and some treatments used in the severe phase of the disease.

361 A randomised open-label phase I/II study adding ONCOS-102 to pemetrexed/cisplatin in patients with unresectable malignant pleural mesothelioma – 12 month analysis of biomarkers and clinical outcomes

BackgroundMalignant pleural mesothelioma (MPM) is a rare, aggressive malignancy without curative treatment. Majority of patients receive pemetrexed/cisplatin as standard of care (SoC). Median overall survival in unresectable disease is 12 months. ONCOS-102 is a granulocyte-macrophage colony stimulating factor (GM-CSF) expressing oncolytic adenovirus (Ad5/3-D24-GMCSF) with a unique ability to both prime and boost immune responses. The aim of the study was to assess immune and clinical responses as well as safety in patients with 1st and 2nd line unresectable MPM.MethodsEligible patients (experimental arm, n=20) received ONCOS-102 given intratumorally under CT or US guidance at a dose of 3 × 10 × 11 on Day 1, 4, 8, 36, 78 and 120 plus six cycles of SoC starting on Day 22. The control group (n=11) received only SoC. Imaging was done at baseline, Day 43–64 and 127–148. Patients were monitored regularly for immunological assessment including lesional biopsies (baseline and Day 36). Primary objective was safety and tolerability. Secondary objectives were immunological activation, ORR, PFS and OS as well as correlation between immunological activation and clinical outcome.ResultsThere were no safety concerns nor DLTs. In 1st line patients ORR/DCR was 30%/90% in the experimental group and 33%/83% in the control group. 2nd line patients had ORR/DCR of 11%/67% in the experimental group and 60%/80% in the control group. 12-month survival rate for the 1st line pts was 64% in the experimental group and 50% in the control group. PFS and OS are still to be reported. The treatment with ONCOS-102 induced strong upregulation of multiple genes associated with immune activation in tumor lesions. Profound innate and adaptive immune activation was observed in the experimental vs control group that was associated with better clinical outcome. In addition to an increase in intra-tumoral cytotoxic T-cells (10/15 pts), the treatment with ONCOS-102 resulted in polarization from M2 to M1 macrophages. An upregulation of PD-L1 was reported in 9/15 pts in the experimental group vs 2/5 pts in the control arm, highlighting the potential of ONCOS-102 as an immunosensitizing agent for combinatory therapies with checkpoint inhibitors.ConclusionsONCOS-102 treated patients benefited from superior immune activation compared to patients receiving SoC with preliminary signals of clinical efficacy. Upregulation of adaptive immunity and cytotoxicity related gene expression, PD-L1 level and M2 to M1 macrophage polarization indicate that ONCOS-102 can induce a favourable TME modulation thus providing a scientific rationale for combination with check point inhibition.Trial RegistrationClinicalTrials. gov NCT02879669Ethics ApprovalThis study was approved by the IRBs of all the sites in Madrid, Barcelona, Rennes and Poitiers.

Immune transcriptomes of highly exposed SARS-CoV-2 asymptomatic seropositive versus seronegative individuals from the Ischgl community

To investigate prevalence of ongoing activation of inflammation following asymptomatic SARS-CoV-2 infection we characterized immune cell transcriptomes from 43 asymptomatic seropositive and 52 highly exposed seronegative individuals with few underlying health issues following a community superspreading event. Four mildly symptomatic seropositive individuals examined three weeks after infection as positive controls demonstrated immunological activation. Approximately four to six weeks following the event, the two asymptomatic groups showed no significant differences. Two seropositive patients with underlying genetic disease impacting immunological activation were included (Cystic Fibrosis (CF), Nuclear factor-kappa B Essential Modulator (NEMO) deficiency). CF, but not NEMO, associated with significant immune transcriptome differences including some associated with severe SARS-CoV-2 infection (IL1B, IL17A, respective receptors). All subjects remained in their usual state of health from event through five-month follow-up. Here, asymptomatic infection resolved without evidence of prolonged immunological activation. Inclusion of subjects with underlying genetic disease illustrated the pathophysiological importance of context on impact of immunological response.

Immune transcriptomes of highly exposed SARS-CoV-2 asymptomatic seropositive versus seronegative individuals from the Ischgl community

To investigate prevalence of ongoing activation of inflammation following asymptomatic SARS-CoV-2 infection we characterized immune cell transcriptomes from 43 asymptomatic seropositive and 52 highly exposed seronegative individuals with few underlying health issues following a community superspreading event. Four mildly symptomatic seropositive individuals examined three weeks after infection as positive controls demonstrated immunological activation. Approximately four to six weeks following the event, the two asymptomatic groups showed no significant differences. Two seropositive patients with underlying genetic disease impacting immunological activation were included (Cystic Fibrosis (CF), Nuclear factor-kappa B Essential Modulator (NEMO) deficiency). CF, but not NEMO, associated with significant immune transcriptome differences including some associated with severe SARS-CoV-2 infection (IL1B, IL17A, respective receptors). All subjects remained in their usual state of health from event through five-month follow-up. Here, asymptomatic infection resolved without evidence of prolonged immunological activation. Inclusion of subjects with underlying genetic disease illustrated the pathophysiological importance of context on impact of immunological response.

Acute Routine Leukocyte and Neutrophil Counts Are Predictive of Poststroke Recovery at 3 and 12 Months Poststroke: An Exploratory Study

Background and Aims. White blood cell (WBC) and neutrophil counts (NC) are common markers of inflammation and neurological stroke damage and could be expected to predict poststroke outcomes. Objective. The aim of this study was to explore the prognostic value of early poststroke WBC and NC to predict cognition, mood, and disability outcomes at 3 and 12 months poststroke. Methods. Routine clinical analyses WBC and NC were collected at 3 time points in the first 4 days of hospitalization from 156 acute stroke patients. Correlations using hierarchical or ordinal regressions were explored between acute WBC and NC and functional recovery, depression, and cognition at 3 and 12 months poststroke, after covarying for age and baseline stroke severity. Results. We found significant increases in NC between <12 hours and 24 to 48 hours time points ( P = .05). Hierarchical regressions, covaried for age and baseline stroke severity, found that 24 to 48 hours WBC ( P = .05) and NC ( P = .04) significantly predicted 3-month cognition scores. Similarly, 24 to 48 hours WBC ( P = .05) and NC ( P = .02) predicted cognition scores at 12 months. Increases in WBC and NC were predictive of increased cognition scores at both 3 and 12 months (positive recovery) though there were no significant associations between WBC and NC and disability or depression scores. Conclusions. Routine acute stroke clinical laboratory tests such as WBC and NC taken between 24 and 48 hours poststroke are predictive of cognition poststroke. It is interpreted that higher rapid immunological activation in the acute phase is an indicator for the trajectory of positive stroke recovery.

Microwave Ablation and Immune Activation in the Treatment of Recurrent Colorectal Lung Metastases: A Case Report

We present a patient with colorectal metastases confined to the lungs and treated with multiple resections until this was not an option anymore, followed by stereotactic body radiation therapy until this option was drained. Then, the patient was successfully treated with multiple microwave ablations combined with immunological activation targeting the programmed cell death 1 receptor (PD-1), possibly instigating a powerful abscopal effect. Techniques, doses, and radiological findings are presented.