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Tumor-immune interaction, surgical treatment, and cancer recurrence in a mathematical model of melanoma.

Eikenberry S, Thalhauser C, Kuang Y - PLoS Comput. Biol. (2009)

Bottom Line: Numerical experiments further suggest that metastatic disease is optimally suppressed by immune activation when the primary tumor is moderately, rather than minimally, metastatic.Furthermore, satellite lesions can become aggressively tumorigenic upon removal of the primary tumor and its associated immune tissue.This can lead to recurrence where total cancer mass increases more quickly than in primary tumor invasion, representing a clinically more dangerous disease state.

View Article: PubMed Central - PubMed

Affiliation: Department of Mathematics and Statistics, Arizona State University, Tempe, Arizona, USA. seikenbe@asu.edu

ABSTRACT
Malignant melanoma is a cancer of the skin arising in the melanocytes. We present a mathematical model of melanoma invasion into healthy tissue with an immune response. We use this model as a framework with which to investigate primary tumor invasion and treatment by surgical excision. We observe that the presence of immune cells can destroy tumors, hold them to minimal expansion, or, through the production of angiogenic factors, induce tumorigenic expansion. We also find that the tumor-immune system dynamic is critically important in determining the likelihood and extent of tumor regrowth following resection. We find that small metastatic lesions distal to the primary tumor mass can be held to a minimal size via the immune interaction with the larger primary tumor. Numerical experiments further suggest that metastatic disease is optimally suppressed by immune activation when the primary tumor is moderately, rather than minimally, metastatic. Furthermore, satellite lesions can become aggressively tumorigenic upon removal of the primary tumor and its associated immune tissue. This can lead to recurrence where total cancer mass increases more quickly than in primary tumor invasion, representing a clinically more dangerous disease state. These results are in line with clinical case studies involving resection of a primary melanoma followed by recurrence in local metastases.

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Related in: MedlinePlus

Resection of a strongly immunogenic tumor followed by low-level metastatic persistence.In this case, the immune response holds the metastatic load to a total mass much less than that of the primary tumor, and unlike in the cases shown in Figures 7 and 8, resection of the primary tumor does not induce growth in these metastases. However, a small but biologically relevant metastatic load remains, suggesting that dormant metastases can persist nearly indefinitely and may be sensitive to future perturbations of the system.
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pcbi-1000362-g009: Resection of a strongly immunogenic tumor followed by low-level metastatic persistence.In this case, the immune response holds the metastatic load to a total mass much less than that of the primary tumor, and unlike in the cases shown in Figures 7 and 8, resection of the primary tumor does not induce growth in these metastases. However, a small but biologically relevant metastatic load remains, suggesting that dormant metastases can persist nearly indefinitely and may be sensitive to future perturbations of the system.

Mentions: Resection can lead to aggressive metastatic recurrence, but in some cases where the immune response is very strong, resection can lead to a state where metastases persist but remain held to a small size. This state of persistence can last indefinitely, and an example is shown in Figure 9.


Tumor-immune interaction, surgical treatment, and cancer recurrence in a mathematical model of melanoma.

Eikenberry S, Thalhauser C, Kuang Y - PLoS Comput. Biol. (2009)

Resection of a strongly immunogenic tumor followed by low-level metastatic persistence.In this case, the immune response holds the metastatic load to a total mass much less than that of the primary tumor, and unlike in the cases shown in Figures 7 and 8, resection of the primary tumor does not induce growth in these metastases. However, a small but biologically relevant metastatic load remains, suggesting that dormant metastases can persist nearly indefinitely and may be sensitive to future perturbations of the system.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2667258&req=5

pcbi-1000362-g009: Resection of a strongly immunogenic tumor followed by low-level metastatic persistence.In this case, the immune response holds the metastatic load to a total mass much less than that of the primary tumor, and unlike in the cases shown in Figures 7 and 8, resection of the primary tumor does not induce growth in these metastases. However, a small but biologically relevant metastatic load remains, suggesting that dormant metastases can persist nearly indefinitely and may be sensitive to future perturbations of the system.
Mentions: Resection can lead to aggressive metastatic recurrence, but in some cases where the immune response is very strong, resection can lead to a state where metastases persist but remain held to a small size. This state of persistence can last indefinitely, and an example is shown in Figure 9.

Bottom Line: Numerical experiments further suggest that metastatic disease is optimally suppressed by immune activation when the primary tumor is moderately, rather than minimally, metastatic.Furthermore, satellite lesions can become aggressively tumorigenic upon removal of the primary tumor and its associated immune tissue.This can lead to recurrence where total cancer mass increases more quickly than in primary tumor invasion, representing a clinically more dangerous disease state.

View Article: PubMed Central - PubMed

Affiliation: Department of Mathematics and Statistics, Arizona State University, Tempe, Arizona, USA. seikenbe@asu.edu

ABSTRACT
Malignant melanoma is a cancer of the skin arising in the melanocytes. We present a mathematical model of melanoma invasion into healthy tissue with an immune response. We use this model as a framework with which to investigate primary tumor invasion and treatment by surgical excision. We observe that the presence of immune cells can destroy tumors, hold them to minimal expansion, or, through the production of angiogenic factors, induce tumorigenic expansion. We also find that the tumor-immune system dynamic is critically important in determining the likelihood and extent of tumor regrowth following resection. We find that small metastatic lesions distal to the primary tumor mass can be held to a minimal size via the immune interaction with the larger primary tumor. Numerical experiments further suggest that metastatic disease is optimally suppressed by immune activation when the primary tumor is moderately, rather than minimally, metastatic. Furthermore, satellite lesions can become aggressively tumorigenic upon removal of the primary tumor and its associated immune tissue. This can lead to recurrence where total cancer mass increases more quickly than in primary tumor invasion, representing a clinically more dangerous disease state. These results are in line with clinical case studies involving resection of a primary melanoma followed by recurrence in local metastases.

Show MeSH
Related in: MedlinePlus