Immunorepertoire-based characterization of adaptive immunity in human malignant pleural effusion

Malignant pleural effusion (MPE) frequently occurs in patients with advanced cancer and is predominantly infiltrated by lymphocytes, particularly CD4⁺ T cells. However, the characteristics of adaptive immune cells, including T-cell receptor (TCR) and B-cell receptor (BCR) repertoires, in MPE remain largely unclear.

In this study, we comprehensively characterized adaptive immune alterations in human lung adenocarcinoma-associated MPE and peripheral blood samples using single-cell RNA sequencing and single-cell V(D)J sequencing.

No significant difference in complementary determining region 3 length distribution was observed among adaptive immune cell subsets between MPE and blood samples. Within MPE microenvironment, regulatory T cells and regulatory B cells preferentially harbored specific V(D)J gene segments, while Th1/17 cells exhibited marked clonal expansion associated with metabolic adaptation, enhanced effector functions, and a propensity to recognize MPE-specific antigens. In addition, expanded cytotoxic CD8⁺ T cells displayed functional heterogeneity characterized by strong cytotoxic potential alongside an exhaustion signature. Notably, our findings underscore the functional importance of TCR complementary determining region 3 in determining MPE-specific antigen recognition. However, no significant clonotypic or functional changes were detected in the BCR repertoire.

This study provides a TCR/BCR-based single-cell atlas of adaptive immune profiles in MPE, offering new insights into the immunopathogenesis of this malignancy-associated condition.