Immune-related pulmonary toxicities of checkpoint inhibitors in non-small cell lung cancer: Diagnosis, mechanism, and treatment strategies

Abstract

Immune checkpoint inhibitors (ICI) therapy based on programmed cell death-1 (PD-1) and programmed cell death ligand 1 (PD-L1) has changed the treatment paradigm of advanced non-small cell lung cancer (NSCLC) and improved the survival expectancy of patients. However, it also leads to immune-related adverse events (iRAEs), which result in multiple organ damage. Among them, the most common one with the highest mortality in NSCLC patients treated with ICI is checkpoint inhibitor pneumonitis (CIP). The respiratory signs of CIP are highly coincident and overlap with those in primary lung cancer, which causes difficulties in detecting, diagnosing, managing, and treating. In clinical management, patients with serious CIP should receive immunosuppressive treatment and even discontinue immunotherapy, which impairs the clinical benefits of ICIs and potentially results in tumor recrudesce. Therefore, accurate diagnosis, detailedly dissecting the pathogenesis, and developing reasonable treatment strategies for CIP are essential to prolong patient survival and expand the application of ICI. Herein, we first summarized the diagnosis strategies of CIP in NSCLC, including the classical radiology examination and the rising serological test, pathology test, and artificial intelligence aids. Then, we dissected the potential pathogenic mechanisms of CIP, including disordered T cell subsets, the increase of autoantibodies, cross-antigens reactivity, and the potential role of other immune cells. Moreover, we explored therapeutic approaches beyond first-line steroid therapy and future direction based on targeted signaling pathways. Finally, we discussed the current impediments, future trends, and challenges in fighting ICI-related pneumonitis.

The impact of pulmonary artery to ascending aorta diameter ratio progression on the prognosis of NSCLC patients treated with immune checkpoint inhibitors

“…Reduced left ventricular function leads to a reduction in aortic diameter. Although right ventricular function may be reduced by ICIs, pulmonary function may also be affected ( 47 ), leading to an increase in right ventricular afterload and subsequent increases in both pulmonary artery pressure and pulmonary artery diameter. An association between ICIs and PAD/AoD ratio progression has been observed previously.…”

Efficacy of immunotherapy in patients with non-small cell lung cancer

“…В заключение хотелось бы отметить, что лечение распространенного НМРЛ остается важнейшей задачей, подталкиваю щей клиницистов двигаться вперед в поисках новых стратегий [29,30]. Появившаяся в арсенале химиотерапевтов ИТ представляется новой парадигмой, улучшаю щей результаты на разных этапах лечения.…”

“…Общая выживаемость в зависимости от линии терапии Progression-free survival by line of therapy МЕДИЦИНСКИЙ СОВЕТ 2023;17(22):[30][31][32][33][34][35][36][37][38][39] …”

Medicine and Psychology: Modern Problems, New Technologies and Ways of Developing Outdated Theories

“…Another condition similar to immune-related pneumonitis is radiation pneumonitis. Such patients always have a history of radiation therapy [368].…”