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7.6Immune Response to Cancer

In the 1950s, Nobel Prize-winning immunologist Barnett proposed the "Immunosurveillance Theory" stating "Multicellular higher organisms such as humans are constantly exposed to the risks of the alteration of multiple genes, and cells in which mutated genes are expressed are recognized and removed by the immune system." Shortly afterwards, a hypothesis that cancer cells are not subject to immune responses as they are autologous became rather prevalent. In the 1970s, substances that activate cells involved in immune response were used as adjuvant cancer therapy. After the year 1990, it became possible to detect immune responses to cancer cells both experimentally and in cancer patients, and to determine an antigen molecule (see Chapter 9) in each individual case. Vaccines utilizing these antigens have been designed, and active attempts are being made to enhance specific immune response.
It is indisputable today that the immune system can recognize cancer cells as nonself, and conversely, cancer cells survive and proliferate by suppressing the immune system through diverse mechanisms. Nevertheless, it appears that some more time is required before cancer treatment strategies making efficient use of vaccines, e.g., the prophylaxis of recurrences and eradication of microscopic metastases, are established as common treatment methods.

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The "Seed and Soil" Hypothesis

In 1889, French surgeon Paget published a hypothesis based on the autopsy results of a number of breast cancer patients that whether or not a cancer metastasizes and to where it metastasizes can be determined by both the properties of the cancer cells themselves (seed factor) from the perspective of histomorphology and the properties of the organs to where the cancer metastasizes (soil factor). In almost all types of cancer including breast carcinoma, organs affected by metastasis are usually not decided solely by anatomical position relationships or by connection manners to blood vessels and lymph channels.
For instance, melanoma, a cancer which generally occurs in the skin, metastasizes frequently to the lung and brain, but when developed in the retina, it metastasizes to the liver. The frequent metastatic destination of digestive system cancers such as stomach cancer, pancreatic cancer, and colorectal cancer is the liver. Prostate cancer metastasizes to the lung and bones. It is also certain that some cancers are more likely to become metastatic while others are not even when their origin is the same. The "Seed and Soil Hypothesis" is therefore accepted as the truth today. However, it cannot be asserted that the mechanism behind the organ specificity of metastasis has sufficiently been elucidated. Cellular chemotactic factors, cell adhesion molecules, and cell growth factors are all assumed to be partly responsible for this. Suspecting that the embryological origin of the organs may have something to do with the frequency of metastasis, researchers have often conducted examinations to delve into that, all to no avail.

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