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Intrapleural Injection of Anti-PD1 Antibody: A Novel Management of Malignant Pleural Effusion.

ABSTRACT:

Background

Malignant tumors accompanied with malignant pleural effusion (MPE) often indicate poor prognosis. The therapeutic effect and mechanism of intrapleural injection of anti-programmed cell death protein 1 (PD1) on MPE need to be explored.

Methods

A preclinical MPE mouse model and a small clinical study were used to evaluate the effect of intrapleural injection of anti-PD1 antibody. The role of immune cells was observed via flow cytometry, RNA-sequencing, quantitative PCR, western blot, immunohistochemistry, and other experimental methods.

Results

Intrathoracic injection of anti-PD1 monoclonal antibody (mAb) has significantly prolonged the survival time of mice (P = 0.0098) and reduced the amount of effusion (P = 0.003) and the number of cancer nodules (P = 0.0043). Local CD8+ T cells participated in intrapleural administration of anti-PD1 mAb. The proportion of CD69+, IFN-γ+, and granzyme B+ CD8+ T cells in the pleural cavity was increased, and the expression of TNF-α and IL-1β in MPE also developed significantly after injection. Local injection promoted activation of the CCL20/CCR6 pathway in the tumor microenvironment and further elevated the expression of several molecules related to lymphocyte activation. Clinically, the control rate of intrathoracic injection of sintilimab (a human anti-PD1 mAb) for 10 weeks in NSCLC patients with MPE was 66.7%. Local injection improved the activity and function of patients' local cytotoxic T cells (CTLs).

Conclusions

Intrapleural injection of anti-PD1 mAb could control malignant pleural effusion and the growth of cancer, which may be achieved by enhancing local CTL activity and cytotoxicity.

SUBMITTER: Li X

PROVIDER: S-EPMC8711587 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionThe staphylococcal enterotoxin C (SEC), a commercially available bio-product from Staphylococcus aureus (S. aureus), has been widely used to control MPE.ObjectivesWe designed and performed a new systematic review (SR) and meta-analysis to clarify the perfusion protocols with SEC, determine their clinical effectiveness and safety, and reveal the indication and optimum usage for achieving the desired responses.MethodologyAll randomized controlled trials (RCTs) about SEC for MPE were collected from electronic databases (from inception until July 2021), and clustered into multiple logical topics. After evaluating their methodological quality, we pooled the data from each topic using the meta-analysis or descriptive analysis, and summarized the evidence quality using the grading of recommendation assessment, development, and evaluation (GRADE) approach.ResultsAll 114 studies were clustered into SEC perfusion alone or plus chemical agents. The SEC alone showed a better complete response (CR), a lower pleurodesis failure, and adverse drug reactions (ADRs), and a higher fever than cisplatin (DDP) alone. The SEC and chemical agents developed 10 perfusion protocols. Among them, only SEC and DDP perfusion showed a better CR, a lower failure, disease progression and ADRs, and a higher fever than DDP alone. The SEC (100-200 ng per time, one time a week for one to four times) with DDP (30-40 mg, or 50-60 mg each time) significantly improved clinical responses for patients with moderate to large volume, Karnofsky performance status (KPS) scores ≥40, ≥50, or ≥60, and anticipated survival time (AST) ≥2 or 3 months. Most results were moderate to low quality.ConclusionCurrent pieces of evidence indicate that super-antigen SEC is a pleurodesis agent, which provides an attractive alternative to existing palliative modalities for patients with MPE. Among 10 protocols, the SEC and DDP perfusion is a most commonly used, which shows a significant improvement in clinical responses with low ADRs. These findings also provide a possible indication and optimal usage for SEC and DDP perfusion.

Project description:Objective:To evaluate the role of intrapleural positioning of a pleural catheter in early lung expansion and pleurodesis success in patients with recurrent malignant pleural effusion (RMPE).Methods:This was a retrospective study nested into a larger prospective cohort study including patients with RMPE recruited from a tertiary university teaching hospital between June of 2009 and September of 2014. The patients underwent pleural catheter insertion followed by bedside pleurodesis. Chest CT scans were performed twice: immediately before pleurodesis (iCT) and 30 days after pleurodesis (CT30). Catheter positioning was categorized based on iCT scans as posterolateral, anterior, fissural, and subpulmonary. We used the pleural volume on iCT scans to estimate early lung expansion and the difference between the pleural volumes on CT30 and iCT scans to evaluate radiological success of pleurodesis. Clinical pleurodesis success was defined as no need for any other pleural procedure.Results:Of the 131 eligible patients from the original study, 85 were included in this nested study (64 women; mean age: 60.74 years). Catheter tip positioning was subpulmonary in 35 patients (41%), anterior in 23 (27%), posterolateral in 17 (20%), and fissural in 10 (12%). No significant differences were found among the groups regarding early lung expansion (median residual pleural cavity = 377 mL; interquartile range: 171-722 mL; p = 0.645), radiological success of pleurodesis (median volume = 33 mL; interquartile range: -225 to 257 mL; p = 0.923), and clinical success of pleurodesis (85.8%; p = 0.676).Conclusions:Our results suggest that the position of the tip of the pleural catheter influences neither early lung expansion nor bedside pleurodesis success in patients with RMPE.Objetivo:Avaliar o papel do posicionamento intrapleural do cateter pleural na expansão pulmonar precoce e no sucesso da pleurodese em pacientes com derrame pleural maligno recorrente (DPMR).Métodos:Trata-se de um estudo retrospectivo aninhado em um estudo prospectivo de coorte maior com pacientes com DPMR recrutados em um hospital-escola universitário terciário entre junho de 2009 e setembro de 2014. Os pacientes foram submetidos a inserção de cateter pleural e, em seguida, pleurodese à beira do leito. A TC de tórax foi realizada duas vezes: imediatamente antes da pleurodese (TCi) e 30 dias após a pleurodese (TC30). Com base na TCi, a posição do cateter foi classificada em posterolateral, anterior, fissural e subpulmonar. Usamos o volume pleural na TCi para estimar a expansão pulmonar precoce e a diferença entre os volumes pleurais na TC30 e na TCi a fim de avaliar o sucesso radiológico da pleurodese. Considerou-se que a pleurodese teve êxito clínico quando não foi necessário realizar nenhum outro procedimento pleural.Resultados:Dos 131 pacientes elegíveis do estudo original, 85 foram incluídos neste estudo aninhado (64 mulheres; média de idade: 60,74 anos). A posição da ponta do cateter foi subpulmonar em 35 pacientes (41%), anterior em 23 (27%), posterolateral em 17 (20%) e fissural em 10 (12%). Não houve diferenças significativas entre os grupos quanto à expansão pulmonar precoce (mediana da cavidade pleural residual = 377 ml; intervalo interquartil: 171-722 ml; p = 0,645), sucesso radiológico da pleurodese (mediana do volume = 33 ml; intervalo interquartil: -225 a 257 ml; p = 0,923) e sucesso clínico da pleurodese (85,8%; p = 0,676).Conclusões:Nossos resultados sugerem que a posição da ponta do cateter pleural não influencia nem a expansão pulmonar precoce nem o sucesso da pleurodese à beira do leito em pacientes com DPMR.