Intratumoral Microbiota Impacts the First-Line Treatment Efficacy and Survival in Non-Small Cell Lung Cancer Patients Free of Lung Infection

Abstract

Background. It has been known that there are microecology disorders during lung cancer development. Theoretically, intratumoral microbiota (ITM) can impact the lung cancer (LC) survival and treatment efficacy. This study conducted a follow-up investigation of non-small cell lung cancer (NSCLC) patients without lung infection to prove whether ITM indeed impacts the first-line treatment efficacy and survival. Methods. We enrolled all patients diagnosed with NSCLC in our department from 2017 to 2019, whose tumor samples were available (through surgery or biopsy) and sent for pathogen-targeted sequencing. All patients received the first-line treatment according to the individual situation. In the short term, the efficacy of the first-line treatment was recorded. During the follow-up, the survival status, progress events, and overall survival (OS) period were recorded if a patient was contacted. Results. Firstly, 53 patients were included, and our following analysis focused on the stage III and stage IV cases with ADC, SCC, or ASC tumors (47 cases). Several bacteria are associated with the LC status and progression, including N stages, metastasis sites, epidermal growth factor receptor (EGFR) mutation, first-line outcome, and later survival. The risk bacteria include Serratia marcescens, Actinomyces neesii, Enterobacter cloacae, and Haemophilus parainfluenzae; and the protective (against LC development and progression) ones include Staphylococcus haemolyticus and Streptococcus crista. In the logistic regression, the two-year survival can be predicted using the results of four bacteria (Haemophilus parainfluenzae, Serratia marcescens, Acinetobacter jungii, and Streptococcus constellation), with an accuracy rate of 90.7%. Conclusion. ITM have links to malignancy, EGFR mutation, first-line outcome, and survival of NSCLC. Our results implied the potential anti-NSCLC activity of antibiotics when used reasonably. It is still necessary to deepen the understanding of the characteristics of ITM and its interactions with NSCLC tumors and the immune cells, which is significant in individualized approaches to the LC treatment.

Profiling of Microbial Landscape in Lung of Chronic Obstructive Pulmonary Disease Patients Using RNA Sequencing

“…37 Staphylococcus haemolyticus is well known for infections in the lungs and has been reported to increase survival after first line treatment, especially in patients with non-small cell lung cancer. 38,39 It was also found in a study of the lung microbiota in patients with idiopathic pulmonary fibrosis. 40 Despite its well-recognized role in the lungs, its function has been poorly understood, with lung cancer being the most studied.…”

Intratumor microbiome: selective colonization in the tumor microenvironment and a vital regulator of tumor biology

“…As a newly found player in the tumor microenvironment, numerous studies have proven that the composition of tumor microbiota is significantly different from that of adjacent normal tissues 12 and is widely associated with clinical features of patients (Table 1). 13–33 These results highlight the potential role of intratumor microbiome in regulating cancer development. Thus, the roles and mechanisms of mutual regulation among intratumor microbiome, tumor cells, and other components of the tumor environment urgently need to be uncovered.…”

The Intratumor Bacterial and Fungal Microbiome Is Characterized by HPV, Smoking, and Alcohol Consumption in Head and Neck Squamous Cell Carcinoma

“…Haemophilus parainfluenzae is a normal oral florum, a known inflammatory agent, and the cause of several acute diseases in the respiratory tract [ 65 ]. Additionally, intratumor Haemophilus parainfluenzae is associated with an increased risk of EGFR+ nonsmall cell lung cancer [ 66 ] and may possibly drive lung cancer oncogenesis through NTHi-driven inflammation [ 67 ]. While our findings suggest that this microbe may play a crucial role in procancer and anticancer pathways, further invitro experiments are needed to reveal which mechanisms modulate its role in oncogenesis in HNSCC.…”