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IMMUNOTHERAPY OF MALIGNANT MELANOMA

Authors
Journal
Surgical Clinics of North America
0039-6109
Publisher
Elsevier
Publication Date
Volume
76
Issue
6
Identifiers
DOI: 10.1016/s0039-6109(05)70520-x
Disciplines
  • Biology
  • Design
  • Medicine

Abstract

In 1908, Paul Erlich proposed the possibility of using the immune system to eradicate tumor. In 1957, Prehn and Main 116 established an animal model for the elimination of methocolanthane-induced sarcomas using adoptive therapy with stimulated lymphocytes against tumor-specific transplantation antigens in syngeneic mice. Subsequently, Thomas 153 postulated the cellular mechanism of tumor rejection, and Burnet 16 introduced the concept of immunologic surveillance of cancer in that the immune system acts as a surveillance mechanism by which newly mutated cancer cells can be eliminated. Based on the animal model of Prehn and Main, it has been the dream of oncologists to stimulate the immune system to reject a growing cancer in humans. In this sense, immunotherapy encompasses any therapeutic modalities utilizing any immune-related agents, such as cytokines, vaccine preparations, cellular or humoral products, with or without immunopotentiation by drugs or other agents. Therapeutic manipulation of the immune system can be broadly designated immunotherapy. Therefore, in terms of cancer immunotherapy, cancer is the target and immunotherapeutic modalities are means to manipulate the immune system to eradicate cancer. To date, immunotherapy is still experimental. With the recent finding that the tumor may be recognized by effector cells, reliable immunotherapeutic approaches may be developed to become effective in the treatment of cancer. Although intense investigation is being pursued in human melanoma and renal cell carcinoma because these two types of cancer may be more immunogenic, the principles derived from such studies may help to develop new frontiers in the immunologic treatment of other types of solid tumor, especially for cancers that have failed conventional treatment modalities such as surgery, chemotherapy, and radiation therapy. Since the description of melanoma in 1787, its biologic behavior has suggested that the immune system may play a significant role in its interaction with melanoma. Several lines of evidence may support this hypothesis: (1) Melanoma has been found to be the cancer second in incidence to neuroblastoma in children with respect to spontaneous regression in documented cases. 32 (2) Approximately 5% of patients with metastatic melanoma have an unknown primary, suggesting that the primary melanoma may have regressed spontaneously. 120 (3) Although widespread vitiligo-like leukoderma is an uncommon clinical entity, its clinical manifestation suggests that immune mechanisms may be the cause of destruction of both normal melanocytes and malignant melanoma. 65 (4) In superficial spreading melanoma, it is not infrequent to appreciate areas of regression with tumor-infiltrating lymphocytes. Lymphocytic infiltration of the primary tumor has been associated with a better prognosis than when the primary tumor is not infiltrated with lymphocytes. 147 Although it is not a common finding, occasionally melanoma may remain dormant for more than 20 years after the diagnosis of the primary melanoma, followed by subsequent recurrence and death caused by melanoma. 13 This may suggest tumor escape following a long period of host tumor interaction. (5) Further, in vitro studies show that malignant melanoma may be immunogenic. 84,130 Based on these findings, there has been a significant effort to treat malignant melanoma using immunologic modalities. More effective therapy is needed, as the incidence of melanoma is doubling every 10 years, 37 and metastatic melanoma is usually resistant to chemotherapy and radiation therapy.

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