Thesis topic proposal
The effect of ionizing radiation on the immune system and its role in the modulation of antitumor immune response


Institute: Semmelweis University, Budapest
clinical medicine
Doctoral School of Pathological Sciences

Thesis supervisor: Katalin Lumniczky
Location of studies (in Hungarian): Országos "Frédéric Joliot Curie" Sugárbiológiai és Sugáregészségügyi Kutató Inté
Abbreviation of location of studies: OFJC

Description of the research topic:

High dose ionizing radiation is a well-known carcinogen. Low dose effects are, however controversial. Due to DNA damaging effect of ionizing radiation an increased tumor incidence following low dose exposure cannot be ruled out. Another potential long-term consequence of low dose exposure is considered the increased incidence of cardiovascular diseases in people occupationally exposed to elevated levels of background radiation. On the other hand, several animal studies point to beneficial health effects of low dose irradiation. The epidemiological significance of low dose exposure drastically increased worldwide during the last decade due to the steep increase in the number of radiological medical interventions for diagnostic purposes. To note, that these interventions are often performed on young, potentially healthy persons with a long prospective lifespan, who, thus, “have enough time” for the development of radiation induced stochastic effects. All these facts justify the urgent need to clarify the long-term consequences of low dose irradiation as well as the identification of risk groups within the population.
Morphological and functional damage of immune cells by ionizing radiation leads to alterations in the antitumor immune response, potentially leading to an increased probability of malignant transformation and tumor development. It also leads to an increase in the incidence of so-called non-cancer effects mainly on the cardiovascular system and the brain. While high dose irradiation has a net immune suppressing effect, low dose effects on the immune system are controversial and not well understood. Local radiotherapy of malignant tumors can influence both the local and regional antitumor immune response and an increasing number of studies point to a positive effect of local radiotherapy in activating systemic antitumor immune responses. The main topic of the project is to study the effect of ionizing radiation on the immune system and to explore the impact of radiation on communication networks between directly irradiated cells and their environment as well as the role of immune system within this process.

Our research project concentrates on the following subtopics:
1. To determine the impact of various doses of ionizing radiation on the functional subunits of the immune system in healthy individuals. For this mice will be exposed to various doses of acute or chronic irradiation and the number as well as functional alterations in various lymphocyte subpopulations will be followed.
2. Since the radiosensitivity of the immune system is greatly influenced by the age when the exposition takes place, we propose to investigate the above mentioned immune parameters in mice irradiated either prenatally or at various times after birth.
3. In order to determine the role of genetic background in the radiosensitivity of the immune system, experiments outlined in point 1 will be performed in mice with different genetic background. We will concentrate on mice with different sensitivity to ionizing radiation, or on mice genetically predisposed to chronic inflammatory reactions or to autoimmune diseases, as well as on immunodeficient mice.
4. Ionizing radiation might not be sufficient to induce a detectable immune activation, but might be able to modulate an already existing immune reaction. In order to test this hypothesis the antitumor immune response of tumor bearing mice will be investigated after local or total-body irradiation.
5. Finally, we propose to investigate the influence of low dose irradiation on tumor take or growth. Healthy mice will be subjected to low dose total-body irradiation followed by tumor transplantation. Tumor take and growth rate, as well as the modulation of antitumor immune response will be followed.

The references of some relevant review articles within the field are enclosed:
Demaria S, Formenti SC. Sensors of ionizing radiation effects on the immunological environment of cancer. Int J Radiat Biol 2007, 83:819-825.
McBride WH, Chiang C, Olson JL et al. A sense of danger from radiation. Radiat Res 2004, 162:1-19.

Number of students who can be accepted: 3

Deadline for application: 2018-09-29

All rights reserved © 2007, Hungarian Doctoral Council. Doctoral Council registration number at commissioner for data protection: 02003/0001. Program version: 2.2358 ( 2017. X. 31. )