Cell-mediated immune responses in paraneoplastic neurological syndromes

Abstract

Paraneoplastic neurological syndromes (PNS) are disorders of the nervous system that are associated with remote effects of malignancy. PNS are considered to have an autoimmune pathology. It has been suggested that immune antitumor responses are the origin of improved outcome in PNS. We describe cell-mediated immune responses in PNS and their potential contributions to antitumor reactions. Experimental and neuropathological studies have revealed infiltrates in nervous tissue and disturbances in lymphocyte populations in both cerebrospinal fluid and peripheral blood. A predominance of cytotoxic T lymphocytes (CTLs) over T helper cells has been observed. CTLs can be specifically aggressive against antigens shared by tumors and nervous tissue. Based on genetic studies, a common clonal origin of lymphocytes from blood, tumor, and nervous tissue is suggested. Suppressive regulatory T (Treg) lymphocytes are dysfunctional. Simultaneously, in tumor tissue, more intense cell-mediated immune responses are observed, which often coincide with a less aggressive course of neoplastic disease. An increased titer of onconeural antibodies is also related to better prognoses in patients without PNS. The evaluation of onconeural and neuronal surface antibodies was recommended in current guidelines. The link between PNS emergence and antitumor responses may result from more active CTLs and less functional Treg lymphocytes.

Figure 1

Lymphocytes of various subpopulations are found in affected regions of the nervous system, cerebrospinal fluid, and blood. The regions of the infiltrates do not always coincide with the area of cell loss that presumably comes from the retrograde degeneration.

Figure 2

The same Hu antigen is present in both nervous tissue and tumor tissue. Cytotoxic T lymphocytes (CTLs) recognizing it are found in tumors and in the peripheral blood and nervous system. The clones of the TCR receptor appear to be similar in all three locations (based on the findings reported in [35, 63]).

Figure 3

Cytotoxic T lymphocytes that are derived from PNS patients appear to be more aggressive towards cells presenting the Hu antigen.