Infections and Immunotherapy in Lung Cancer: A Bad Relationship?

Abstract

Infectious diseases represent a relevant issue in lung cancer patients. Bacterial and viral infections might influence the patients’ prognosis, both directly affecting the immune system and indirectly impairing the outcome of anticancer treatments, mainly immunotherapy. In this analysis, we aimed to review the current evidence in order to clarify the complex correlation between infections and lung cancer. In detail, we mainly explored the potential impact on immunotherapy outcome/safety of (1) bacterial infections, with a detailed focus on antibiotics; and (2) viral infections, discriminating among (a) human immune-deficiency virus (HIV), (b) hepatitis B/C virus (HBV-HCV), and (c) Sars-Cov-2. A series of studies suggested the prognostic impact of antibiotic therapy administration, timing, and exposure ratio in patients treated with immune checkpoint inhibitors, probably through an antibiotic-related microbiota dysbiosis. Although cancer patients with HIV, HBV, and HCV were usually excluded from clinical trials evaluating immunotherapy, some retrospective and prospective trials performed in these patient subgroups reported similar results compared to those described in not-infected patients, with a favorable safety profile. Moreover, patients with thoracic cancers are particularly at risk of COVID-19 severe outcomes and mortality. Few reports speculated about the prognostic implications of anticancer therapy, including immunotherapy, in lung cancer patients with concomitant Sars-Cov-2 infection, showing, to date, inconsistent results. The correlation between infectious diseases and immunotherapy remains to be further explored and clarified in the context of dedicated trials. In clinical practice, the accurate and prompt multidisciplinary management of lung cancer patients with infections should be encouraged in order to select the best treatment options for these patients, avoiding unexpected toxicities, while maintaining the anticancer effect.

Risk of Infection with Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis

“…The increased risk of infection when ICIs were administered with CT was probably due to the synergistic effects of each agents' specific toxicities, such as pneumonitis (from ICIs), neutropenia (CT and targeted agents), the advanced stage of the disease, and the diagnosis of a lung cancer [ 46 ]. Remarkably, regarding this tumor, the occurrence of infections might influence the patient’s prognosis, as shown by the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), which causes the severe Coronavirus disease 19 (COVID-19) and a higher risk of mortality.…”

Lung adenocarcinoma with active pulmonary tuberculosis: a case report of successful immunotherapy and systematical review

“…LC complicated with pulmonary tuberculosis is a special group, and most of these patients are excluded from the research on ICIs. Recent research has shown that antibiotic-induced disruption of the microbiota may impact ICI e cacy [7][8][9][10] . A systematic review and meta-analysis of study displayed [11] that despite the high heterogeneity between studies, OS still revealing a signi cantly reduced survival in patients with NSCLC exposed to antibiotics.…”

Impact of concomitant idiopathic pulmonary fibrosis on prognosis in lung cancer patients: A meta-analysis

“…of infection or dysbiosis due to their treatment, which was proved to affect the prognosis of lung cancer [52,53]. In general, concomitant IPF may promote development and progression through underlying mechanisms that were formerly mentioned.…”