Pathogen spectrum and management strategies for opportunistic infections in lung cancer in the immunotherapy era: recent advances from fungi to mycobacteria.

Lung cancer is one of the most common cancers and the leading cause of cancer death worldwide. Opportunistic infections (OI) are increasingly recognized in this population due to disease-related immune dysfunction and treatment-induced immunosuppression. Compared with the chemotherapy era, the use of immune checkpoint inhibitors and targeted agents has shifted the OI profile. Pneumocystis jirovecii pneumonia (PJP) and invasive pulmonary aspergillosis (IPA) are reported more often in older adults and patients with lymphopenia, while tuberculosis (TB) and nontuberculous mycobacteria (NTM) cluster in those with structural lung disease (e.g., bronchiectasis, cavities) and prolonged immunosuppression. High-risk features include absolute lymphocyte count <500/µL, corticosteroids ≥20 mg prednisone-equivalent for ≥4 weeks, airway obstruction, prior TB, chronic obstructive pulmonary disease/interstitial lung disease (ILD), and recent broad-spectrum antibiotics. Diagnosis should integrate high-resolution computed tomography (HRCT) patterns (e.g., diffuse ground-glass for PJP; nodules with halo sign for IPA), microbiology [bronchoalveolar lavage fluid (BALF) culture/microscopy, galactomannan (GM)/β-D-glucan (BDG)], and metagenomic next-generation sequencing, interpreted against host factors and treatment timeline, while carefully distinguishing immune-related pneumonitis and TKI-associated ILD. Prophylaxis with TMP-SMX is recommended for high-risk patients; voriconazole (or isavuconazole) is first-line for IPA with attention to drug-drug interactions; TB/NTM regimens require coordination with anticancer therapy, especially where rifamycins interact with TKIs. Vaccination (influenza, pneumococcus, zoster) and antimicrobial stewardship are essential. Future work should validate risk scores prospectively and clarify microbiome-immunotherapy-infection relationships.