A

FIGURE 17-1 Lymphocytic inflammation associated with certain tumors. A, Medullary breast carcinoma. B, Malignant melanoma. Red arrows indicate malignant cells. Yellow arrows indicate lymphocyte-rich inflammatory infiltrates.

FIGURE 17-1 Lymphocytic inflammation associated with certain tumors. A, Medullary breast carcinoma. B, Malignant melanoma. Red arrows indicate malignant cells. Yellow arrows indicate lymphocyte-rich inflammatory infiltrates.

Medullary breast carcinoma

Malignant melanoma of the skin

Medullary breast carcinoma

Malignant melanoma of the skin lymphocytic infiltrates in some types of melanoma and carcinomas of the colon and breast cancer is predictive of a better prognosis. The first experimental demonstration that tumors can induce protective immune responses came from studies of transplanted tumors performed in the 1950s (Fig. 17-2). A sarcoma may be induced in an inbred mouse by painting its skin with the chemical carcinogen methylcholanthrene (MCA). If the MCA-induced tumor is excised and transplanted into other syngeneic mice, the tumor grows. In contrast, if the tumor is transplanted back into the original host, the mouse rejects the tumor. The same mouse that had become immune to its tumor is incapable of rejecting MCA-induced tumors produced in other

Mouse with chemical carcinogen-induced tumor

Mouse with chemical carcinogen-induced tumor

Transplant tumor cells Transplant tumor cells into original Tumor into syngeneic mouse tumor-bearing mouse cells

Adoptively transfer T cells into recipient of tumor transplant

Adoptively transfer T cells into recipient of tumor transplant

FIGURE 17-2 Experimental demonstration of tumor immunity. Mice that have been surgically cured of a chemical carcinogen (MCA)-induced tumor reject subsequent transplants of the same tumor, whereas the transplanted tumor grows in normal syngeneic mice. The tumor is also rejected in normal mice that are given adoptive transfer of T lymphocytes from the original tumor-bearing animal.

No tumor growth

Tumor growthj

Eradication of tumor

FIGURE 17-2 Experimental demonstration of tumor immunity. Mice that have been surgically cured of a chemical carcinogen (MCA)-induced tumor reject subsequent transplants of the same tumor, whereas the transplanted tumor grows in normal syngeneic mice. The tumor is also rejected in normal mice that are given adoptive transfer of T lymphocytes from the original tumor-bearing animal.

mice. Furthermore, T cells from the tumor-bearing animal can transfer protective immunity to the tumor to another tumor-free animal. Thus, immune responses to tumors exhibit the defining characteristics of adaptive immunity, namely, specificity, memory, and the key role of lymphocytes. As predicted from these transplantation experiments, the most effective response against naturally arising tumors appears to be mediated mainly by T lymphocytes.

• Immune responses frequently fail to prevent the growth of tumors. There may be several reasons that antitumor immunity is unable to eradicate transformed cells. First, tumor cells are derived from host cells and resemble normal cells in many respects. Therefore, most tumors tend to be weakly immunogenic. Tumors that elicit strong immune responses include those induced by oncogenic viruses, in which the viral proteins are foreign antigens, and tumors induced in animals by potent carcinogens (such as methylcholan-threne), which often cause mutations in normal cellular genes. Many spontaneous tumors induce weak or even undetectable immunity, and studies of such tumors led to considerable skepticism about the concept of immune surveillance. It is now clear that the importance of immune surveillance and tumor immunity varies with the type of tumor. Second, the rapid growth and spread of tumors may overwhelm the capacity of the immune system to effectively control a tumor, which requires that all the malignant cells be eliminated. Third, many tumors have specialized mechanisms for evading host immune responses. We will return to these mechanisms later in the chapter.

• The immune system can be activated by external stimuli to effectively kill tumor cells and eradicate tumors. As we shall see at the end of the chapter, this realization has spurred new directions in tumor immunotherapy in which augmentation of the host anti-tumor response is the goal of treatment.

The existence of specific antitumor immunity implies that tumors must express antigens that are recognized as foreign by the host. The nature and significance of these antigens are described next.

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