Combining surgery and immunotherapy: turning an immunosuppressive effect into a therapeutic opportunity

Abstract Background Cancer surgery is necessary and life-saving. However, the majority of patients develop postoperative recurrence and metastasis, which are the main causes of cancer-related deaths. The postoperative stress response encompasses a broad set of physiological changes that have evolved to safeguard the host following major tissue trauma. These stress responses, however, intersect with cellular mediators and signaling pathways that contribute to cancer proliferation. Main Previous descriptive and emerging mechanistic studies suggest that the surgery-induced prometastatic effect is linked to impairment of both innate and adaptive immunity. Existing studies that combine surgery and immunotherapies have revealed that this combination strategy is not straightforward and patients have experienced both therapeutic benefit and drawbacks. This review will specifically assess the immunological pathways that are disrupted by oncologic surgical stress and provide suggestions for rationally combining cancer surgery with immunotherapies to improve immune and treatment outcomes. Short conclusion Given the prevalence of surgery as frontline therapy for solid cancers, the emerging data on postoperative immunosuppression and the rapid development of immunotherapy for oncologic treatment, we believe that future targeted studies of perioperative immunotherapy are warranted

Treatment of primary Sjögren syndrome.

International audiencePrimary Sjögren syndrome (pSS) is a progressive autoimmune disease characterized by sicca and systemic manifestations. In this Review, we summarize the available data on topical and systemic medications, according to clinical signs and disease activity, and we describe the ongoing studies using biologic drugs in the treatment of pSS. Expanding knowledge about the epidemiology, classification criteria, systemic activity scoring (ESSDAI) and patient-reported outcomes (ESSPRI) is driving active research. Treatment decisions are based on the evaluation of symptoms and extraglandular manifestations. Symptomatic treatment is usually appropriate, whereas systemic treatment is reserved for systemic manifestations. Sicca is managed by education, environment modification, elimination of contingent offending drugs, artificial tears, secretagogues and treatments for complications. Mild systemic signs such as fatigue are treated by exercise. Pain can require short-term moderate-dose glucocorticoid therapy and, in some cases, disease-modifying drugs. Severe and acute systemic manifestations indicate treatment with glucocorticoids and/or immunosuppressant drugs. The role for biologic agents is promising, but no double-blind randomized controlled trials (RCTs) proving the efficacy of these drugs are available. Targets for new treatments directed against the immunopathological mechanisms of pSS include epithelial cells, T cells, B-cell overactivity, the interferon signature, proinflammatory cytokines, ectopic germinal centre formation, chemokines involved in lymphoid cell homing, and epigenetic modifications