1059P - Tertiary lymphoid structures localization and maturation heterogeneities correlate with divergent clinical outcomes and immune responses 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 pathological conditions. However, the clinical implications of localization and maturation stage of TLS in clear cell renal cell carcinoma (ccRCC) remain to be elucidated.

Methods

Immunohistochemistry and multispectral fluorescent were used to evaluate the TLS heterogeneity along with TME cell-infiltrating characterizations. We comprehensively assessed the prognostic and immunological implications of the TLS heterogeneity in 625 patients with ccRCC from multiply cohorts. Associations between TLS heterogeneity and immunologic activities were assessed by the quantification of immune cells infiltration.

Results

TLS typically comprises B-cell follicles with germinal centers and are surrounded by T-cell zones and dendritic cells. TLS infiltrates were identified in 34.2% of the ccRCC samples. A higher proportion of early TLS was found in peritumoral TLS, while intratumoral TLS mainly comprised secondary follicle-like. Kaplan-Meier analyses indicated that the presence of intratumoral TLS markedly correlated with both superior progression-free survival PFS and OS, while the presence of peritumoral TLS showed the opposite predictive trends for outcomes. Notably, presence of TLS, especially intratumoral TLS and mature TLS (namely SFL-TLS, with CD23⁺ germinal center) significantly correlated with better clinical outcomes and objective reflection rate for ccRCC patients receiving immunotherapies. 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 peritumoral regions increased prominently, showing a typical suppressive TME characterizations.

Conclusions

In conclusion, this study for the first time revealed the implications of TLS localization and maturation heterogeneity on the clinical outcomes and immunological status and responses of ccRCC, allowing the identification of immunophenotypes and the improvement of immunotherapeutic effectiveness for ccRCC.

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.