In cancer patients, the immune system is often altered with an excess of inhibitory factors, such as immunosuppressive cytokines, produced by regulatory T cells (Treg) or myeloid-derived suppressor cells (MDSC). The manipulation of the immune system has emerged as one of new promising therapies for cancer treatment, and also represents an attractive strategy to control prostate cancer (PCa). Therapeutic cancer vaccines and immune checkpoint inhibitors have been the most investigated in clinical trials. Many trials are ongoing to define the effects of immune therapy with established treatments: androgen deprivation therapy (ADT) and chemotherapy (CT) or radiotherapy (RT). This article discusses some of these approaches in the context of future treatments for PCa.
Prostate cancer (PCa) is the second most common cancer in men. As well in many other human cancers, inflammation and immune suppression have an important role in their development. We briefly describe the host components that interact with the tumor to generate an immune suppressive environment involved in PCa promotion and progression. Different tools provide to overcome the mechanisms of immunosuppression including vaccines and immune checkpoint blockades. With regard to this, we report results of most recent clinical trials investigating immunotherapy in metastatic PCa (Sipuleucel-T, ipilimumab, tasquinimod, Prostvac-VF, and GVAX) and provide possible future perspectives combining the immunotherapy to the traditional therapies.
Primary antibody deficiencies (PADs) are the most common primary immunodeficiencies (PIDs). They can be divided into the following groups, depending on their immunological features: agammaglobulinemia; common variable immunodeficiency (CVID) isotype; hyper IgM isotype; light chain or functional deficiencies with normal B cell count; specific antibody deficiency with normal Ig concentrations and normal numbers of B cells and transient hypogammaglobulinemia of infancy. The role of vaccination in PADs is recognized as therapeutic, diagnostic and prognostic and may be used in patients with residual B-cell function to provide humoral immunity to specific infective agents. According to their content and mechanisms, vaccines are grouped as live attenuated, inactivated (conjugated, polysaccharide), mRNA or replication-deficient vector vaccines. Vaccination may be unsafe or less effective when using certain vaccines and in specific types of immunodeficiency. Inactivated vaccines can be administered in PAD patients even if they could not generate a protective response; live attenuated vaccines are not recommended in major antibody deficiencies. From December 2020, European Medicines Agency (EMA) approved vaccines against COVID-19 infection: according to ESID advises, those vaccinations are recommended in patients with PADs. No specific data are available on safety and efficacy in PAD patients.
Hepatitis C virus (HCV) causes B cell lymphoproliferative disorders including mixed cryoglobulinemia vasculitis (MCV) and indolent non-Hodgkin lymphomas (NHL); both disorders regress in a large proportion of cases when HCV infection is cleared by antiviral therapy. 1 Before the advent of direct-acting antivirals (DAAs), the cornerstone of anti-HCV therapy was pegylated interferon (IFN) in association with ribavirin. However, with IFN/ribavirin a sustained virological response (SVR) was achieved only in about half of HCV-MCV patients, 2-4 while DAAs yield nearly 100% SVR. 5-10 The overall response rate of MCV are similar in patients who attained a SVR after either IFN-based, 88%-97%, 3,4 or IFN-free therapy, average 93%. 5-9 However, recent studies reported that 4%-11% of DAAtreated patients with clinical response of MCV have relapse of vasculitis despite remaining in SVR, 7,9,10 while very few relapses of vasculitis have been described in IFN-treated patients who did not have virological relapse. 11,12 Also, serum cryoglobulins have been reported to persist for at least several months in 20%-50% of SVR patients after DAAs 5,7,8 while, to our knowledge, such observation is lacking in reports on IFN-based therapy.
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