Purpose: Myeloid-derived suppressor cells (MDSC) are considered an important T-cell immunosuppressive component in cancer-bearing hosts. The factors that attract these cells to the tumor microenvironment are poorly understood. IL8 (CXCL8) is a potent chemotactic factor for neutrophils and monocytes.Experimental Design: MDSC were characterized and sorted by multicolor flow cytometry on ficoll-gradient isolated blood leucokytes from healthy volunteers (n ¼ 10) and advanced cancer patients (n ¼ 28). In chemotaxis assays, sorted granulocytic and monocytic MDSC were tested in response to recombinant IL8, IL8 derived from cancer cell lines, and patient sera. Neutrophil extracellular traps (NETs) formation was assessed by confocal microscopy, fluorimetry, and time-lapse fluorescence confocal microscopy on short-term MDSC cultures.Results: IL8 chemoattracts both granulocytic (GrMDSC) and monocytic (MoMDSC) human MDSC. Monocytic but not granulocytic MDSC exerted a suppressor activity on the proliferation of autologous T cells isolated from the circulation of cancer patients. IL8 did not modify the T-cell suppressor activity of human MDSC. However, IL8 induced the formation of NETs in the GrMDSC subset.Conclusions: IL8 derived from tumors contributes to the chemotactic recruitment of MDSC and to their functional control.

Changes in serum IL-8 levels could be used to monitor and predict clinical benefit from immune checkpoint blockade in melanoma and NSCLC patients.

Purpose: Interleukin-8 (IL8) is a chemokine produced by malignant cells of multiple cancer types. It exerts various functions in shaping protumoral vascularization and inflammation/immunity. We evaluated sequential levels of serum IL8 in preclinical tumor models and in patients to assess its ability to estimate tumor burden.Experimental Design: IL8 levels were monitored by sandwich ELISAs in cultured tumor cells supernatants, tumor-xenografted mice serum, and in samples from 126 patients with cancer. We correlated IL8 serum levels with baseline tumor burden and with treatment-induced changes in tumor burden, as well as with prognosis.Results: IL8 concentrations correlated with the number of IL8-producing tumor cells in culture. In xenografted neoplasms, IL8 serum levels rapidly dropped after surgical excision, indicating an accurate correlation with tumor burden. In patients with melanoma (n ¼ 16), renal cell carcinoma (RCC; n ¼ 23), non-small cell lung cancer (NSCLC; n ¼ 21), or hepatocellular carcinoma (HCC; n ¼ 30), serum IL8 concentrations correlated with tumor burden and stage, survival (melanoma, n ¼ 16; RCC, n ¼ 23; HCC, n ¼ 33), and objective responses to therapy, including those to BRAF inhibitors (melanoma, n ¼ 16) and immunomodulatory monoclonal antibodies (melanoma, n ¼ 8). IL8 concentrations in urine (n ¼ 18) were mainly elevated in tumors with direct contact with the urinary tract.Conclusions: IL8 levels correlate with tumor burden in preclinical models and in patients with cancer.

Poly I:C is a powerful immune adjuvant as a result of its agonist activities on TLR-3, MDA5 and RIG-I. BO-112 is a nanoplexed formulation of Poly I:C complexed with polyethylenimine that causes tumor cell apoptosis showing immunogenic cell death features and which upon intratumoral release results in more prominent tumor infiltration by T lymphocytes. Intratumoral treatment with BO-112 of subcutaneous tumors derived from MC38, 4 T1 and B16-F10 leads to remarkable local disease control dependent on type-1 interferon and gamma-interferon. Some degree of control of non-injected tumor lesions following BO-112 intratumoral treatment was found in mice bearing bilateral B16-OVA melanomas, an activity which was enhanced with co-treatment with systemic anti-CD137 and anti-PD-L1 mAbs. More abundant CD8 + T lymphocytes were found in B16-OVA tumor-draining lymph nodes and in the tumor microenvironment following intratumoral BO-112 treatment, with enhanced numbers of tumor antigen-specific cytotoxic T lymphocytes. Genome-wide transcriptome analyses of injected tumor lesions were consistent with a marked upregulation of the type-I interferon pathway. Inspired by these data, intratumorally delivered BO-112 is being tested in cancer patients (NCT02828098). Electronic supplementary material The online version of this article (10.1186/s40425-019-0568-2) contains supplementary material, which is available to authorized users.

This radio-immunotherapy combination strategy, aimed at resembling viral infection in tumor tissue in combination with a dendritic-cell vaccine and SABR, is safe and shows immune-associated activity and signs of preliminary clinical efficacy.

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Background and Aim Endoscopic ultrasonography (EUS)‐guided drainage (EUS‐D) has become the standard treatment for peripancreatic fluid collections. Its use in other intra‐abdominal abscesses has been reported, although there is limited evidence. Methods We carried out a single‐center retrospective cohort study comparing percutaneous drainage (PCD) and EUS‐D of upper abdominal abscesses between January 2012 and June 2017. Pancreatic fluid collections and liver transplant recipients were excluded. Primary endpoints were technical and clinical success rates. Results We included 18 EUS‐D (nine hepatic and nine intraperitoneal abscesses) and 62 PCD. There were no differences regarding age, gender and etiology. Size was larger in the PCD group (80 vs 65.5 mm, P = 0.04) and perivesicular location was more frequent in the PCD group (24.2% vs 11.1%, P = 0.003). In the EUS‐D group, metal stents were deployed in 16 (88.9%) subjects (eight lumen‐apposing metal stents and eight self‐expandable metal stents), coaxial double‐pigtail plastic stents in six (33.3%) and lavage/debridement was carried out in five (27.8%). There were no significant differences in technical success (EUS‐D: 88.9%, PCD: 96.8%, P = 0.22) or clinical success (EUS‐D: 88.9%, PCD: 82.3%, P = 0.50), with no relapses in the EUS‐D group and 10 (16.1%) in the PCD group (P = 0.11). There were four (22.2%) adverse events in the EUS‐D group, none of them severe, and 13 (21%) in the PCD group (P = 0.91). Conclusions EUS‐D is an alternative to PCD in the treatment of upper abdominal abscesses, reaching similar success, relapse and adverse events rates.

Surgically resectable synchronic and metachronic liver metastases of colon cancer have high risk of relapse in spite of standard-of-care neoadjuvant and adjuvant chemotherapy regimens. Dendritic cell vaccines loaded with autologous tumor lysates were tested for their potential to avoid or delay disease relapses (NCT01348256). Patients with surgically amenable liver metastasis of colon adenocarcinoma (n = 19) were included and underwent neoadjuvant chemotherapy, surgery and adjuvant chemotherapy. Fifteen patients with disease-free resection margins were randomized 1:1 to receive two courses of four daily doses of dendritic cell intradermal vaccinations versus observation. The trial had been originally designed to include 56 patients but was curtailed due to budgetary restrictions. Follow-up of the patients indicates a clear tendency to fewer and later relapses in the vaccine arm (median disease free survival –DFS-) 25.26 months, 95% CI 8.74-n.r) versus observation arm (median DFS 9.53 months, 95% CI 5.32–18.88).Electronic supplementary materialThe online version of this article (10.1186/s40425-018-0405-z) contains supplementary material, which is available to authorized users.