IMMUNOLOGY - Roitt I. - Mir 2000

Chapter 20. Tumor Immunology

IMMUNODIAGNOSIS

Although only a small number of markers are known to be strictly unique to tumor Cells, Antibodies against tumor-associated Antigens can be extremely useful for diagnostic purposes. They allow the detection of elevated levels of a particular antigen or the presence of an antigen in an unusual Location. Therefore, antigens used for Diagnosis do not necessarily have to be tumor-specific.

In vivo. Radiolabeled antibodies against tumor-associated antigens are used for in vivo tumor detection (Fig. 20.14); however, this method is often less sensitive than modern computed tomography or Magnetic Resonance imaging. Furthermore, immunoscintigraphy has the disadvantage that the antibodies used must be freshly radiolabeled for each patient, and optimal antibodies vary depending on the tumor type. The sensitivity of immunoscintigraphy could be enhanced in the future through The production of recombinant high-affinity antibody fragments.

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Fig. 20.14. Chest radiograph and immunoscintigraphic scan of a patient with colorectal carcinoma and lung and Liver metastases. Human colon tumor-specific Monoclonal Antibodies YPC2/12.1 react with carcinoembryonic antigen (CEA) (a glycoprotein with a molecular mass of 180 kDa). The antibodies were radiolabeled with ¹³¹I and administered intravenously. Scintigrams were obtained after 48 h. The image is shown with Background staining removed, which was caused by non-specific binding of Blood antibodies. (Photographs kindly provided by Prof. C. Sokora).

In vitro. Antibodies can be used to determine the cellular origin of undifferentiated tumors (Fig. 20.15) and to detect micrometastases in Bone Marrow, CEREBROSPINAL FLUID, Lymphoid Organs, etc. (Fig. 20.16). Immunoassay Methods have also been developed to detect multiple tumor-associated antigens in blood serum. Such antigens include, for example, carcinoembryonic antigen (CEA) and α-fetoprotein (AFP). Elevated levels of these antigens can serve as a useful diagnostic indicator; however, neither AFP nor CEA is exclusively associated with a single tumor type, and thus their measurement is primarily important for monitoring Treatment efficacy (Fig. 20.17).

Fig. 20.15. Identification of the cellular origin of an undifferentiated tumor. Routine histological examination of a tumor biopsy (1) revealed undifferentiated tumor cells that could not be identified by this method alone. Staining the tumor by the indirect immunoperoxidase method (2) using antibodies against CD45 (leukocyte common antigen) showed a distinct positive result (brown staining), indicating that the tumor is a lymphoma.

Fig. 20.16. Detection of micrometastases using monoclonal antibodies. Photomicrograph of an impression smear of cells from a Lymph node draining a malignant tumor site. The smear was stained for alkaline phosphatase using an immunological method with cytokeratin-specific antibodies. Carcinoma cells express cytokeratins, and a large, pink-stained tumor Cell is clearly visible in the smear. Routine Cytological examination can easily miss rare tumor cells such as the one shown in this lymph node smear.

Fig. 20.17. Correlation between serum CEA levels and clinical manifestations in a patient with colorectal carcinoma. CEA levels drop following surgery, and a subsequent rise is detected earlier than clinical signs of metastasis can be observed.