Immunological Investigations

Intranodal Administration of Neoantigen Peptide-loaded Dendritic Cell Vaccine Elicits Epitope-specific T Cell Responses and Clinical Effects in a Patient with Chemorefractory Ovarian Cancer with Malignant Ascites

Chemorefractory ovarian cancer has limited therapeutic options. Hence, new types of treatment including neoantigen-specific immunotherapy need to be investigated. Neoantigens represent promising targets for personalized cancer immunotherapy. We here describe the clinical and immunological effects of a neoantigen peptide-loaded DC-based immunotherapy in a patient with recurrent and chemoresistant ovarian cancer. A 71-year-old female patient with chemorefractory ovarian cancer and malignant ascites received intranodal vaccination of DCs loaded with four neoantigen peptides that were predicted by our immunogenomic pipeline. Following four rounds of vaccinations with this therapy, CA-125 levels were remarkably declined and tumor cells in the ascites were also decreased. Concordantly, the tumor-related symptoms such as respiratory discomfort improved without any adverse reactions. The reactivity against one HLA-A2402-restricted neoantigen peptide derived from a mutated PPM1 F protein was detected in lymphocytes from peripheral blood by IFN-γ ELISPOT assay. Furthermore, the neoantigen (PPM1 F mutant)-specific TCRs were detected in the tumor-infiltrating T lymphocytes post-vaccination. Our results showed that vaccination with intranodal injection of neoantigen peptide-loaded DCs may have clinical and immunological impacts on cancer treatment.

The Development of Human Papillomavirus (HPV) Vaccines and Current Barriers to Implementation

The identification of the human papillomavirus (HPV) as the causative agent of multiple cancers allowed for the development of vaccines and immunization strategies to prevent cancers caused by HPV infection. The public health ramifications of reduction of HPV disease burden are momentous in scope. Vaccine hesitancy has impacted widespread vaccination, but strategies have been identified to combat vaccine safety and efficacy misinformation and promote immunization.

IL-6 and IL-8 as Prognostic Factors in Peritoneal Fluid of Ovarian Cancer

The objectives of the study were to analyze the dosage of a cytokine panel (IL2, IL5, IL6, IL8, IL10, and TNF-α) in the peritoneal fluid and relate the dosage of these cytokines to prognostic para- meters and survival in ovarian cancer. Peritoneal fluid was collected intraopera- tively from 29 patients with primary malignant ovarian neoplasia. Cytokine panel dosing was performed with ELISA. Comparisons of cytokines with prognostic factors were performed using the Wilcoxon-Mann-Whitney test. ROC curves were used to determine the cutoff value of NLR, PLR, and IL6. Univariate and multivariate analysis of disease-free survival (DFS) or overall survival (OS) were performed (Kaplan-Meier and Cox regression). The differences were considered significant when the value of p 3.18 (p = .04), a platelet-lymphocyte ratio (PLR) >219.23 (p = .0051), CA-125 levels >35 U/mL (p = .0019), stage IIIC (p = .0203), and DFS ≤ 24 months (p = .0267). For IL-8, higher levels were related to PLR > 219.23 (p = .0426), and CA-125 >35 U/mL (p = .0292). In the univariate analysis, IL-6 levels ≥87.23 in peritoneal fluid had a relationship with shorter DFS at significance threshold (p = .05), and with a shorter OS (p = .039). Multivariate survival analysis proved that IL-6 level in the peritoneal fluid was an independent predictor of OS. Therefore, IL-6 and IL-8 in peritoneal lavage were related to poor prognostic factors. These cytokines may represent new biomarkers for ovarian cancer therapies.

Lymphocytes in Peritumoral Stroma: Evaluation in Epithelial Ovarian Neoplasms

Expression and Clinical Significance of KLRG1 and 2B4 on T Cells in the Peripheral Blood and Tumour of Patients with Cervical Cancer

Killer cell lectin-like receptor G1 (KLRG1) and 2B4 play important roles in the immune regulation and immune tolerance to tumor cells by inhibiting T cell function. However, the clinical relevance of KLRG1 and 2B4 to cervical cancer remains to be understood. We measured the frequency of KLRG1+ or 2B4+ cells in CD4+ or CD8 + T cells derived from peripheral blood or tumour biopsies in cervical cancer patients by flow cytometry. Compared with healthy controls, the level of KLRG1 and 2B4 on CD8 + T cells in the blood of the patients increased significantly ( KLRG1 level on T cells was related to age and HPV in patients with cervical cancer, while 2B4 level on T cells was related to age, underlying their roles in the host immune response to cervical cancer. Radiotherapy can improve the immune function of patients.

The Putative Effects of Neoadjuvant Chemotherapy on the Immune System of Advanced Epithelial Ovarian Carcinoma

The epithelial ovarian carcinoma (EOC) is one of leading causes of cancer-related mortality in females. For some patients, complete resection cannot be achieved, thus neoadjuvant chemotherapy (NACT) following interval debulking surgery (IDS) could be an alternative choice. In general-held belief, cytotoxic chemotherapy is assumed to be immunosuppressive, because of its toxicity to dividing cells in the bone marrow and peripheral lymphoid tissues. However, increasing evidence highlighted that the anticancer activity of chemotherapy may also be related to its ability to act as an immune modulator. NACT not only changed the morphology of cancer cells, but also changed the transcriptomic and genomic profile of EOC, induced proliferation of cancer stem-like cells, gene mutation, and tumor-related adaptive immune response. This review will provide a comprehensive overview of recent studies evaluating the impact of NACT on cancer cells and immune system of advanced EOC and their relationship to clinical outcome. This information could help us understand the change of immune system during NACT, which might provide new strategies in future investigation of immuno-therapy for maintenance treatment of EOC.

Endometriosis: What is the Influence of Immune Cells?

The Role of Stroma in Ovarian Cancer