1905P - Heterogeneity in tertiary lymphoid structures predicts the distinct prognosis and immune microenvironment of clear cell renal cell carcinoma

Background

Tertiary lymphoid structures (TLS) are organized aggregates of immune cells that form postnatally in non-lymphoid tissues and arise under physiological conditions. However, the clinical and immunological implications of heterogeneous subpopulations of TLS in clear cell renal cell carcinoma (ccRCC) remain to be elucidated.

Methods

H&E, immunohistochemistry and 12-marker multispectral fluorescent were used to evaluate the spatial location and maturation status of TLS with TME cell-infiltrating characterizations. We comprehensively assessed the prognostic value of TLS heterogeneity in 395 patients with ccRCC from two independent cohorts using log-rank tests, Cox hazards models, and scoring nomograms. Associations between TLS heterogeneity and immunologic activity of TME were assessed using quantified lymphocytes infiltration fraction.

Results

By pathological review, TLS were identified in 34.2% of the ccRCC samples. For ccRCC patients, the presence of intratumoral TLS markedly correlated with both superior progression-free survival (PFS) and overall survival (OS), while the peritumoral TLS exerted the opposite predictive trend of clinical outcomes. Multivariate Cox analysis revealed that the presence of intratumoral TLS was prominently correlated with better outcomes. Additionally, the novel nomograms incorporating the presence of intratumoral TLS prominently predicted the probability of 8-year PFS and OS of ccRCC (AUC >0.80). Moreover, a higher proportion of early TLS was found in peritumoral TLS (P=0.016), while intratumoral TLS were mainly composed of secondary follicle-like TLS (P=0.004). Interestingly, in ccRCC samples with the presence of peritumoral TLS enriched with primary follicle-like TLS, the proportion of PD-L1⁺ tumor-associated macrophages and Treg infiltration in the stroma were prominently increased, showing a typical suppressive tumor immune microenvironment.

Conclusions

In conclusion, this study revealed the predictive value of TLS heterogeneity on the progression and immunological responses of ccRCC for the first time. The intratumoral TLS could be used to assess both the prognostic patterns and the unique TME characteristics of each patient.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.