Page 64 - 2014 Printable Abstract Book
P. 64
transient T reg cell ablation with radiotherapy for the management of poorly immunogenic, aggressive
malignancies.
2
1
(S1404) Role of interferons in anti-tumor effects of radiation. Edith Lord ; Kelli A. Connolly ; Joanne Y.H.
2
2
1
Lim, PhD ; and Scott A. Gerber, Ph.D, Univ of Rochester Medical Center, Rochester, NY and Univ of
Rochester Medical Center, Rochester, NY
2
Radiation therapy (RT) continues to be a key treatment modality for many types of cancer. However there
is individual variation in the response to therapy. Some patients are nonresponders whose disease
continues to progress, whereas others are responders and treatment results in tumor control or cure. The
realization that the immune system is involved in many of the anti-tumor effects of RT has heightened the
interest in better understanding the interplay between radiation and immune cells within the tumor
microenvironment. We have developed a novel murine tumor model that mimics the clinical
phenomenon of responders/nonresponders in which C57/BL6 mice bearing colon38, a colon
adenocarcinoma are treated locally with 15 Gy RT. By monitoring immune parameters including
numbers/types of intratumoral immune cells and levels of type II interferon-gamma (IFN-[[Unsupported
Character - Symbol Font γ]]), we are able to distinguish the two response phenotypes within the first few
days following treatment. Responders were characterized by increased levels of IFN-[[Unsupported
+
Character - Symbol Font γ]] that appear to license CD8 T cells to actively lyse the tumor cells, whereas
this response was diminished in tumors unresponsive to RT. Based on its known ability to stimulate IFN-
[[Unsupported Character - Symbol Font γ]], we tested the efficacy of the immunomodulatory cytokine, IL-
12 in combination with IR treatment and found that this resulted in a 100% cure rate. In a second tumor
model (B16 melanoma) we have found that type I IFNs can also enhance the efficacy of radiation therapy.
Our pre-clinical studies clearly demonstrate that the efficacy of RT depends upon the immune response
and that immunotherapy designed to further stimulate immunity can enhance the effectiveness of RT.
S15 ORIGIN AND MECHANISM OF RADIATION CARCINOGENESIS
Radiation-induced cancer is one of the most important late effects of ionizing radiation. The Symposium
will start with a discussion on the biological basis of cancer using breast as a model. Other leading
investigators will discuss the modulating roles of caspases, aberrant DNA repair and the non-targeted
effect in radiation carcinogenesis.
(S1501) The Role Epigenetic Reprogramming in the Neoplastic Transformation of Human Breast
Epithelial Cells. Jose Russo, Fox Chase Cancer Center, Philadelphia, PA
Cancer progression can be epigenetically controlled by targeting epigenetic processes that are critical for
the expression of epithelial mesenchymal transition (EMT) phenotypes such as DNA methylation, histone
deacetylation and histone 3 (H3) methylation at lysines 9 and 27, which ensure transcriptional
suppression. Two different approaches have emerged as promissory for epigenetic control of cancer
progression: The first approach involves reversal of DNA hypermethylation and associated gene silencing
through the use of the DNA methyltransferase (DNMT) inhibitors 5-azacytidine (azacitidine) and 5-aza-2′-
deoxycytidine (DAC, decitabine), two hypomethylating cytosine analogues that have been approved by
the USA Food and Drug Administration for treatment of acute myelogenous leukemia and myelodysplastic
62 | P a g e
malignancies.
2
1
(S1404) Role of interferons in anti-tumor effects of radiation. Edith Lord ; Kelli A. Connolly ; Joanne Y.H.
2
2
1
Lim, PhD ; and Scott A. Gerber, Ph.D, Univ of Rochester Medical Center, Rochester, NY and Univ of
Rochester Medical Center, Rochester, NY
2
Radiation therapy (RT) continues to be a key treatment modality for many types of cancer. However there
is individual variation in the response to therapy. Some patients are nonresponders whose disease
continues to progress, whereas others are responders and treatment results in tumor control or cure. The
realization that the immune system is involved in many of the anti-tumor effects of RT has heightened the
interest in better understanding the interplay between radiation and immune cells within the tumor
microenvironment. We have developed a novel murine tumor model that mimics the clinical
phenomenon of responders/nonresponders in which C57/BL6 mice bearing colon38, a colon
adenocarcinoma are treated locally with 15 Gy RT. By monitoring immune parameters including
numbers/types of intratumoral immune cells and levels of type II interferon-gamma (IFN-[[Unsupported
Character - Symbol Font γ]]), we are able to distinguish the two response phenotypes within the first few
days following treatment. Responders were characterized by increased levels of IFN-[[Unsupported
+
Character - Symbol Font γ]] that appear to license CD8 T cells to actively lyse the tumor cells, whereas
this response was diminished in tumors unresponsive to RT. Based on its known ability to stimulate IFN-
[[Unsupported Character - Symbol Font γ]], we tested the efficacy of the immunomodulatory cytokine, IL-
12 in combination with IR treatment and found that this resulted in a 100% cure rate. In a second tumor
model (B16 melanoma) we have found that type I IFNs can also enhance the efficacy of radiation therapy.
Our pre-clinical studies clearly demonstrate that the efficacy of RT depends upon the immune response
and that immunotherapy designed to further stimulate immunity can enhance the effectiveness of RT.
S15 ORIGIN AND MECHANISM OF RADIATION CARCINOGENESIS
Radiation-induced cancer is one of the most important late effects of ionizing radiation. The Symposium
will start with a discussion on the biological basis of cancer using breast as a model. Other leading
investigators will discuss the modulating roles of caspases, aberrant DNA repair and the non-targeted
effect in radiation carcinogenesis.
(S1501) The Role Epigenetic Reprogramming in the Neoplastic Transformation of Human Breast
Epithelial Cells. Jose Russo, Fox Chase Cancer Center, Philadelphia, PA
Cancer progression can be epigenetically controlled by targeting epigenetic processes that are critical for
the expression of epithelial mesenchymal transition (EMT) phenotypes such as DNA methylation, histone
deacetylation and histone 3 (H3) methylation at lysines 9 and 27, which ensure transcriptional
suppression. Two different approaches have emerged as promissory for epigenetic control of cancer
progression: The first approach involves reversal of DNA hypermethylation and associated gene silencing
through the use of the DNA methyltransferase (DNMT) inhibitors 5-azacytidine (azacitidine) and 5-aza-2′-
deoxycytidine (DAC, decitabine), two hypomethylating cytosine analogues that have been approved by
the USA Food and Drug Administration for treatment of acute myelogenous leukemia and myelodysplastic
62 | P a g e
