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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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Metastatic growth under different values of .The primary tumor is held to a steady state by the immune response, and metastases are seeded beginning 6 months into the simulation. For the lowest value of , a single metastatic lesion forms; moderate to high values lead to suppression of all metastases, while a very high  overwhelms the immune response, leading to widespread metastatic growth. Note that in (C) and (D) the immune response to the metastases can cause perturbations in the primary tumor size, but does not change the overall behavior. (A) . (B) . (C) . (D) .
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pcbi-1000362-g010: Metastatic growth under different values of .The primary tumor is held to a steady state by the immune response, and metastases are seeded beginning 6 months into the simulation. For the lowest value of , a single metastatic lesion forms; moderate to high values lead to suppression of all metastases, while a very high overwhelms the immune response, leading to widespread metastatic growth. Note that in (C) and (D) the immune response to the metastases can cause perturbations in the primary tumor size, but does not change the overall behavior. (A) . (B) . (C) . (D) .

Mentions: Numerical investigation has yielded a somewhat nonintuitive result concerning the rate at which metastases are seeded. In a sensitivity analysis of , we have found that for low values of a single secondary metastasis usually forms. Upon increasing to fairly large values, significant metastatic spread occurs, but it is eliminated by the immune response. Very large values of cause metastatic disease to overwhelm the immune response and invade widely. We note that the initial secondary metastasis generally occurs at a predictable distance from the primary tumor, just beyond the range in which the immune response directed against the primary tumor can incidentally suppress metastases. Figure 10 shows the results under several values of .


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

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

Metastatic growth under different values of .The primary tumor is held to a steady state by the immune response, and metastases are seeded beginning 6 months into the simulation. For the lowest value of , a single metastatic lesion forms; moderate to high values lead to suppression of all metastases, while a very high  overwhelms the immune response, leading to widespread metastatic growth. Note that in (C) and (D) the immune response to the metastases can cause perturbations in the primary tumor size, but does not change the overall behavior. (A) . (B) . (C) . (D) .
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Related In: Results  -  Collection

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

pcbi-1000362-g010: Metastatic growth under different values of .The primary tumor is held to a steady state by the immune response, and metastases are seeded beginning 6 months into the simulation. For the lowest value of , a single metastatic lesion forms; moderate to high values lead to suppression of all metastases, while a very high overwhelms the immune response, leading to widespread metastatic growth. Note that in (C) and (D) the immune response to the metastases can cause perturbations in the primary tumor size, but does not change the overall behavior. (A) . (B) . (C) . (D) .
Mentions: Numerical investigation has yielded a somewhat nonintuitive result concerning the rate at which metastases are seeded. In a sensitivity analysis of , we have found that for low values of a single secondary metastasis usually forms. Upon increasing to fairly large values, significant metastatic spread occurs, but it is eliminated by the immune response. Very large values of cause metastatic disease to overwhelm the immune response and invade widely. We note that the initial secondary metastasis generally occurs at a predictable distance from the primary tumor, just beyond the range in which the immune response directed against the primary tumor can incidentally suppress metastases. Figure 10 shows the results under several values of .

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