The production of autoantibodies to self antigens is dependent on the failure of immune tolerance. Cancer cells express antigens which elicit a spontaneous immune response in cancer patients. The repertoire of autoantibodies found in cancer patients partly covers that of patients with autoimmune diseases. Biological activities of autoantibodies to self antigens may induce paraneoplastic syndromes which reflect the attempt of cancer patients to counteract tumor growth. Autoantibodies with similar specificities may have different effects in cancer and autoimmune disease patients due to different immunological microenvironments. Tregs dysfunction has been observed in patients with paraneoplastic syndromes and/or with autoimmune diseases, while the increase of Tregs has been associated with poor cancer patients prognosis. Novel therapies have employed antibodies against Tregs immune-checkpoint receptors with the aim to boost immune response in cancer patients. The presence of autoantibodies to tumors antigens has also been investigated as a marker for cancer detection and cancer patients prognosis. This report reviews the current knowledge on the analysis and meaning of autoantibodies to self antigens detected in cancer and autoimmune disease patients.

Human T-cell leukemialymphoma virus (HTLV) is a type C retrovirus associated with a subtype of mature T-cell malignancy in humans. HTLV also infects normal human cord blood mature T lymphocytes in vitro and induces a number of phenotypic changes in these cells, including their continuous growth and partial or complete independence of T-cell growth factor (TCGF). As part of our initial study designed to analyze gene(s) specifically activated by HTLV infection, we have isolated a recombinant DNA clone by differential screening of a cDNA library made from mRNA of a human T-cell lymphoma cell line producing HTLV. This cDNA identifies a single-copy gene in all human DNAs and a single mRNA species of 2.3 Idlobases expressed at several hundred copies per cell in five HTLV-positive neoplastic T-cell lines. In addition, cord blood T lymphocytes infected with HTLV, but not the uninfected counterparts, express high levels of mRNA from this gene. A survey of different human hematopoietic cell types showed that this gene is expressed at low or undetectable levels (<10 copies) in human T, B, myeloid, or erythroid cell lines; in moderate amounts in lymphoid precursor (immature) cell lines; and in high amounts in lectin-activated mature T-cells, comparable to those of HTLV-infected T-cell lines. The precise function of this gene has not yet been determined.Human T-cell leukemia-lymphoma virus (HTLV) is a unique exogenous retrovirus associated with a subtype ofmature T-cell malignancy in man (1-4). Extensive seroepidemiological studies (5-9) indicate that HTLV is present worldwide but is more prevalent in certain areas, including southwest Japan, the Caribbean, certain parts of South America, and the southeastern United States. There are now at least a dozen isolates of HTLV obtained from patients from different parts of the world (unpublished data). The isolates were obtained from neoplastic mature T-cell lines grown in suspension culture by addition of T-cell growth factor (TCGF) (10). Some ofthese lines eventually became autonomous producers of TCGF (11). Recent experiments indicate that some strains of HTLV can immortalize normal cord blood T lymphocytes in vitro (refs. 12 and 13; unpublished data), resulting in cell cultures that are completely or partially independent of TCGF. This result suggests a role of HTLV in modulation of specific steps in T-cell proliferation, possibly involving TCGF.To study the genes that are expressed at high levels in HTLVinfected cells, we constructed a cDNA library from mRNA of a cutaneous T-cell lymphoma line producing HTLV. The library was screened with homologous cDNA and cDNA synthesized on mRNA of another cutaneous T-cell lymphoma line that is negative for HTLV (14,15). From these experiments we identified a gene that is expressed at high levels in all HTLV-infected cells examined, including five neoplastic lines and two samples of normal cord blood T lymphocytes infected and transformed by HTLV in vitro. Studies on the expression of this gene in a variety of uninfected human...

Head and neck cancer (HNC) has frequently an aggressive course for the development of resistance to standard chemotherapy. Thus, the use of innovative therapeutic drugs is being assessed. Bortezomib is a proteasome inhibitor with strong in vitro and in vivo anticancer effects. In vitro antitumoral activity of Bortezomib was investigated employing human pharynx (FaDu), tongue (SCC-15, CAL-27), salivary gland (A-253) cancer cell lines and a murine cell line (SALTO-5) originated from a salivary gland adenocarcinoma arising in BALB-neuT male mice transgenic for the oncogene neu. Bortezomib in vivo effects in BALB-neuT mice transplanted with murine SALTO-5 cells were also examined. Bortezomib inhibited cells proliferation, triggered apoptosis, modulated the expression and activation of pro-survival signal transduction pathways proteins activated by ErbB receptors and inhibited proteasome activity in vitro. Furthermore, intraperitoneal administration of Bortezomib delayed tumor growth of SALTO-5 cells transplanted in BALB-neuT mice and protracted mice survival. Our findings further support the use of Bortezomib for the treatment of HNC and reveal its ineffectiveness in counteracting the activation of deregulated specific signaling pathways in HNC cell lines when resistance to proteasome inhibition is developed.