Peripheral Blood Oxygen Saturation: A Non-invasive Prognostic Marker in Cancer Patients Treated with Radiation Therapy- A Pilot Study

Aims: 1. To evaluate the prognostic value of SpO2 in cancer patients 2. To correlate between daily SpO2 values and tumor response to radiation. Background: Tumor hypoxia is an important prognostic factor in Oncology. It plays an important role in tumorogenesis, radiation resistance and tumor progression. Many invasive and in-vitro methods are available to assess the hypo-oxygenated status of tumors. Objective: We evaluated if SpO2 values measured from pulse oximetry could be used as an adjunct prognostic and predictive factor in oncology patients. Methods: Ten consecutive patients with locally advanced, non-metastatic disease were evaluated. Daily SpO2 measurements throughout the treatment and weekly haemoglobin values were noted. All patients received radical intent radiation therapy. Patients were categorised into two groups: poor SpO2 (<97mmHg) and better SpO2 (≥98mmHg). Results: Tumour response was higher in patients with better SpO2 (≥98mmHg). Patients with poor SpO2 (<97mmHg) presented with bulkier disease at diagnosis. Conclusion: Role of SpO2 as a prognostic and predictive factor should be explored further with in vitro and pH studies.

Myeloid-derived Suppressor Cells in Cancer: A Review on the Pathogenesis and Therapeutic Potentials

Myeloid-Derived Suppressor Cells (MDSCs) are multifarious group of immature cells that arise from the myeloid and amass in individuals with cancer, sepsis, burns, or chronic inflammation. It has been evidenced that these group of cells are efficient in modifying adaptive and innate immune responses, coherent with their assumed key biological roles. It is evidenced that MDSCs inter-communicate with Tumor-Associated Macrophages (TAM), Tumor-Associated Neutrophils (TAN), Dendritic Cells (DCs), Receptor for Advanced Glycation End-products (RAGE), Toll-Like Receptors (TLRs), Matrix Metalloproteinase (MMPs) as well as High Mobility Group Box 1 (HMGB1) during carcinogenesis. This interaction although elaborated in various studies and reviews still does not explain in details as to how their interplay results in cancer pathogenesis. We noted that MDSC contributed to cancer immune suppressionviaTLR-4 receptor and lipopolysaccharideas (LPS). Furthermore, MDSC contributed to cancer developmentviaMMPs (MMP-9 and MMP1-12) as well as RAGE. In the cancer microenvironment, HMGB1-driven MDSC amassment expedites cancer development and metastasisviaPMN-MDSCs, macrophages, DCs and Immature Myeloid Cells (IMC). Also, HMGB1 intermediation with MDSCsviaRAGE and/or TLR-4 leading to cancer development. Nevertheless, MDSCs have already proven potent in some cancers and are currently been used as treatment options although further studies are needed in some other cancers. Our review, therefore, explores the pivotal pathogenic and therapeutic roles of MDSCs in cancer.

The Antitumor Immunity Mediated by NK Cells: The Role of The NCRs

Natural Killer (NK) cells are innate immune lymphocytes that are important for early and effective immune responses against infections and cancer. The antitumor immunity mediated by NK cells can be exerted through several direct or indirect “immunosurveillance” mechanisms that control tumor growth and prevent the rapid dissemination of metastatic tumors. NK cells express an array of activating and inhibitory receptors that enable them to recognize and bind non-self as well as self-ligands expressed on the surface of malignant or virally infected cells. The family of Natural Cytotoxicity Receptors (NCRs) comprises three activating receptors; NKp30, NKp44, and NKp46 that are important for the stimulation of NK cell effector functions. This review summarizes the mechanisms of antitumor immunity mediated by natural killer cells with focus on the role of the family of the NCRs and their tumor associated ligands.

Nivolumab Induced Acute Severe Toxicity in Lung Adenocarcinoma

Background: Immunotherapy has recently revolutionized the world of oncology. Nivolumab an IgG4 targeting PD-1 receptor has been approved in metastatic melanoma, renal cell carcinoma, Hodgkin lymphoma and non-small cell lung cancer. It works as a checkpoint inhibitor, allowing the immune system to clear cancer, and it is this mechanism of action which explains its toxicity also named as immmune-related adverse events. Case Presentation: This report describes the case of a 65-year-old female with metastatic lung adenocarcinoma treated with nivolumab. After 19º cycle she presented acute severe toxicity with pneumonitis, hypophisitis and thrombocytopenia. She was successfully treated with high dose steroids and immunoglobulins. Conclusion: Immune-related adverse events associated with nivolumab are usually nonspecific, with lots of differential diagnosis. They often resolve with prompt management, however, they may get severe if treatment is not retired and systemic immunosupression with corticosteroids is initiated. As shown in this case, we must be attentive throughout the treatment and even after the end of the treatment, since not all cases occur according to what is described in the literature.

Transforming Growth Factor-Beta1 and Myeloid-Derived Suppressor Cells Interplay in Cancer

Background: Transforming growth factor-beta1 (TGF-β1) is a pleiotropic cytokine with a double role in cancer through its capacity to inhibit early stages of tumors while enhancing tumor progression at late stages of tumor progression. Moreover, TGF-β1 is a potent immunosuppressive cytokine within the tumor microenvironment that allows cancer cells to escape from immune surveillance, which largely contributes to the tumor progression. Method: It has been established that the cancer progression is commonly associated with increased number of Myeloid-derived suppressor cells (MDSC) that are a hallmark of cancer and a key mechanism of immune evasion. Result: MDSC represent a population of heterogeneous myeloid cells comprised of macrophages, granulocytes and dendritic cells at immature stages of development. MDSC promote tumor progression by regulating immune responses as well as tumor angiogenesis and cancer metastasis. Conclusion: In this review, we present an overview of the main key functions of both TGF-β1 and MDSC in cancer and in the immune system. Furthermore, the mutual contribution between TGF-β1 and MDSC in the regulation of immune system and cancer development will be analyzed.

Correlations of Hormone Receptors (ER and PR), Her2/neu and p53 Expression in Breast Ductal Carcinoma Among Yemeni Women

Aims: The purpose of this study was to determine if any relationship exists between Estrogen Receptor (ER),Progesterone Receptor (PR), Her2/neu, P53, and clinicopathological factors in female breast ductal carcinoma. Materials and Methods: One hundred and thirty seven (IDC=124, NIDC=13) ductal carcinomas were clinicopathologically and immunohistochemically analyzed and compared with 20 control cases of benign breast lesions in which assessment of Her-2/neu, ER, PR, and P53 has been performed, prospectively. Chi-square analysis was then used to correlate the above observations. Results: The overall immunoexpression of ER, PR, Her2/neu and P53 were 43.8%, 27%, 30.6% and 48.9%, respectively, of the 137 ductal carcinomas. A significant Positive association between ER or PR expression with lymph node involvement was found ( p= 0.004, p= 0.022 respectively), while p53 was found to be negatively associated with lymph nodes involvement (p= 0.03, 0.02, respectively). P53 also associated negatively to lymph node status (P=0.03) and positively with borderline tumor grade (p= 0.03). Conclusion: There are high rates of positive expression of ER, PR, Her2/neu and P53 among Yamani women with breast ductal carcinoma.

Treatment of Brain Tumors Using DNA-Based Vaccines

Antigenic differences between normal and malignant cells of the cancer patient form the rationale for clinical immunotherapeutic strategies. Because the antigenic phenotype of neoplastic cells varies widely among different cells within the same malignant cell-population, immunization with a vaccine that stimulates immunity to the broad array of tumor antigens expressed by the cancer cells is likely to be more efficacious than immunization with a vaccine for a single antigen. A vaccine prepared by transfer of DNA from the tumor into a highly immunogenic cell line can encompass the array of tumor antigens that characterize the patient’s neoplasm. Poorly immunogenic tumor antigens, characteristic of malignant cells, can become strongly antigenic if they are expressed by highly immunogenic cells. A DNA-based vaccine was prepared by transfer of genomic DNA from a breast cancer that arose spontaneously in a C3H/He mouse into a highly immunogenic mouse fibroblast cell line, where genes specifying tumor-antigens were expressed. The fibroblasts were modified in advance of DNA-transfer to secrete an immune augmenting cytokine and to express allogeneic MHC class I-determinants. In an animal model of breast cancer metastatic to the brain, introduction of the vaccine directly into the tumor bed stimulated a systemic cellular anti-tumor immune response measured by two independent in vitro assays and prolonged the lives of the tumor-bearing mice. Furthermore, using antibodies against the various T-cell subsets, it was determined that the systemic cellular anti-tumor immunity was mediated by CD8+, CD4+ and NK/LAK cells. In addition an enrichment strategy has also been developed to increase the proportion of immunotherapeutic cells in the vaccine which has resulted in the development of enhanced anti-tumor immunity. Finally regulatory T cells (CD4+CD25+Fox p3+-positive) were found to be relatively deficient in the spleen cells from the tumor-bearing mice injected intracerebrally with the enriched vaccine. The application of DNA-based genomic vaccines for the treatment of a variety of brain tumors is being explored.

Tumor-DNA Based Vaccines Fail to Induce Autoimmune Disease in Mice

Allogeneic cellular cancer vaccines that express tumor antigens specified by tumor-DNA have been found to be effective in the treatment of mice with intracerebral breast cancer, a metastasis model system. The vaccines were prepared by the transfer of genomic DNA from a spontaneously arising adenocarcinoma of the mammary gland into a mouse fibroblast cell line (LM). The immunity in tumor-bearing mice treated by immunization with the DNA-based vaccines was specific for the type of tumor from which the DNA was obtained. It was driven mainly by CD8+ T-cells. Here, we present data indicating that animals receiving the therapeutic vaccines failed to exhibit signs of autoimmunity, as indicated by an examination of various H/E stained organs and tissues including brain for infiltrating inflammatory cells and by the absence of serum anti-nuclear antibody (ANA) in the immunized mice. In addition, tumors derived from the vaccine itself failed to develop in immune-competent tumor-free mice injected with the non-irradiated allogeneic vaccines alone.