Ana Bela Sarmento

Lung cancer: the immune system and radiation.

ABSTRACT Lung cancer has a known relationship with smoking and is one of the leading causes of cancer-related death worldwide. Although the number of studies discussing lung cancer is vast, treatment efficacy is still suboptimal due to the wide range of factors that affect patient outcome. This review aims to collect information on lung cancer treatment, specially focused on radiation therapy. It also compiles information regarding the influence of radiotherapy on the immune system and its response to tumour cells. It evaluates how immune cells react after radiation exposure and the influence of their cytokines in the tumour microenvironment. The literature analysis points out that the immune system is a very promising field of investigation regarding prognosis, mostly because the stromal microenvironment in the tumour can provide some information about what can succeed in the future concerning treatment choices and perspectives. T cells (CD4+ and CD8+), interleukin-8, vascular endothelial growth factor and transforming growth factor-β seem to have a key role in the immune response after radiation exposure. The lack of large scale studies means there is no common consensus in the scientific community about the role of the immune system in lung cancer patients treated with radiotherapy. Clarification of the mechanism behind the immune response after radiation can lead to better treatments and better quality life for patients.

The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation.

Immune surveillance seems to represent an effective tumor suppressor mechanism. However, some cancer cells survive and become variants, being poorly immunogenic and able to enter a steady-state phase. These cells become functionally dormant or remain hidden clinically throughout. Neoplastic cells seem to be able to instruct immune cells to undergo changes promoting malignancy. Radiotherapy may act as a trigger of the immune response. After radiotherapy a sequence of reactions occurs, starting in the damage of oncogenic cells by multiple mechanisms, leading to the immune system positive feedback against the tumor. The link between radiotherapy and the immune system is evident. T cells, macrophages, Natural Killer cells and other immune cells seem to have a key role in controlling the tumor. T cells may be dysfunctional and remain in a state of T cell exhaustion, nonetheless, they often retain a high potential for successful defense against cancer, being able to be mobilized to become highly functional. The lack of clinical trials on a large scale makes data a little robust, in spite of promising information, there are still many variables in the studies relating to radiation and immune system. The clarification of the mechanisms underlying immune response to radiation exposure may contribute to treatment improvement, gain of life quality and span of patients.

Radiotherapy Effects on Immune System of Patients with Solid and Hematopoietic Tumors

Background: Radiotherapy (RT) recruits biological effectors outside the treatment field with systemic effects. Non-cancerous cells surrounding the tumor may play a pivotal role in cancer progression, as well as in metastasis. Local radiation triggers systemic effects, which in combination with immunotherapy may contribute to better treatment outcomes. Objective: The aim of this study was to evaluate RT effects on peripheral immune system (IS) in patients with lung cancer (LC) or diffuse large B cell lymphoma (DLBCL) after external beam radiotherapy. Methods: We studied a group of LC and DLBCL patients immediately before RT (T0), half-treatment (T1) and 30 days after the end of treatment (T2). Blood samples were analyzed by flow cytometry for CD3, CD4, CD8, CD19, CD56, CD25, CD127 FoxP3 expression. Procarta Cytokine Profiling kit was used to quantify cytokines and chemokines concentrations. Results: In LC patients, a decrease in B, Natural Killer (NK) and cytotoxic NK cells were observed during treatment, associated with an increase of interleukin (IL)-27 and IL-7 from T0 to T1 and followed by a decrease at T2. DLBCL patients showed increased levels of induced regulatory T cells from T1 to T2 and interferon gamma (INF-γ) over time. Comparing the two pathologies, we perceived that LC patients had increased cell subpopulation levels of IL-1β, IL-2, INF-γ, IL-5 and chemokine (C-C motif) ligand 5 compared to DLBCL patients. Conclusions: RT induces different IS responses between LC and DLBCL patients. Generally, the IS status of the patients at the beginning of the treatment can contribute to different RT treatment responses.

Monoclonal Gammopathies of Indetermined Significance: Diagnosis and Clinical Follow-up Guidelines

The Portuguese group of multiple myeloma of the Portuguese Society of Hematology proposes a national protocol for diagnosis and clinical follow-up of monoclonal gammopathies. The proposed protocol aims to standardize clinical management of monoclonal gammopathies. Furthermore, it would also define the major risk factors for progression to Multiple Myeloma that require a precocious close articulation between general practitioners and a Hematology Clinic.

Obesity and breast cancer: inflammatory and adipocytokine correlations

Obesity is a chronic disease affecting millions of individuals around the world and has taken epidemic proportions. Often, obesity is associated with other risk factors such as hypertension and dyslipidemia, increasing metabolic syndrome- related complications. Such complications include several cancer types, namely breast cancer. Several mechanisms are likely to be involved in cancer development and progression, however obesity as been proved to be a risk factor. This study was designed in order to analyse metabolic, inflammatory and oxidative stress correlations between obesity and breast cancer, studying three groups of patients: obesity, breast cancer and obesity plus breast cancer. Our results revealed no significant metabolic changes between groups, despite some increased glycemia and lipid levels were observed in obesity plus cancer group. Furthermore, obesity plus cancer patients showed increased fasting insulin levels and insulin resistance. Regarding inflammatory biomarkers there were observed no differences in TNF-alpha, IL-6, IL-8 and IL-10. However, MCP-1 levels were found to be increased in obese patients with cancer, suggesting an involvement in obesity- associated tumours. Serum levels of adiponectin were similar in all groups and leptin levels were directly correlated with the BMI. However, resistin levels were increased in obese plus cancer group following MCP-1 profile. This work revealed some biological markers of breast cancer in obese woman, suggesting dysfunctional adipose tissue as the link between obesity and cancer.

Cr(VI)-induced malignant transformation of a bronchial epithelial cell line association with altered mitochondria and bioenergetic phenotypes

Dissertacao de mestrado em Bioquimica apresentada ao Departamento de Ciencias da Vida da Faculdade de Ciencias e Tecnologia da Universidade de Coimbra