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The sharing of molecules function that affects both tumor growth and neoangiogenesis with cells of the immune system creates a mutual interplay that impairs the host's immune response against tumor progression. Increasing evidence shows that tumors are able to create an immunosuppressive microenvironment by recruiting specific immune cells. Moreover, molecules produced by tumor and inflammatory cells in the tumor microenvironment create an immunosuppressive milieu able to inhibit the development of an efficient immune response against cancer cells and thus fostering tumor growth and progression. In addition, the immunoediting could select cancer cells that are less immunogenic or more resistant to lysis. In this review, we summarize recent findings regarding the immunomodulatory effects and cancer progression of the angiogenic growth factor namely placental growth factor (PlGF) and address the biological complex effects of this cytokine. Different pathways of the innate and adaptive immune response in which, directly or indirectly, PlGF is involved in promoting tumor immune escape and metastasis will be described. PlGF is important for building up vascular structures and functions. Although PlGF effects on vascular and tumor growth have been widely summarized, its functions in modulating the immune intra-tumoral microenvironment have been less highlighted. In agreement with PlGF functions, different antitumor strategies can be envisioned.

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.

Poxvirus-based vaccines have a long record of efficacy as both anti-tumour agents and vectors for gene therapy in different human tumour models. Interestingly, several studies of these vaccines have now entered the clinical evaluation phase for safety and effectiveness. A desirable outcome of antigen specific cancer immunotherapy is the disruption of host self-tolerance against endogenous tumour-associated antigens (TAAs). Nonetheless, recent studies have found reductions in vaccine efficacy due to host anti-vaccine immune reactions. Thus, newer approaches bringing together poxvirus-based vaccination and immunostimulation are being developed, and new poxvirus strains are being examined in tumour therapy studies. Our review summarizes the current knowledge on the efficacy of poxvirus-based vaccination on human tumours, with a particular focus on approaches aimed at increasing innate and specific immune responses. Special attention will be devoted to the new poxvirus strains that are currently under consideration for tumour therapy; the current knowledge on clinical trials and outcomes will also be reviewed.