Abstract 293P
Background
Tertiary lymphoid structures (TLS) are organized aggregates of immune cells that form under pathological conditions. However, the predictive value of TLS in clear cell renal cell carcinoma (ccRCC) for immunotherapies remain unclear.
Methods
Immunohistochemistry and multispectral fluorescent were used to evaluate the location and maturation status of TLS with TME cell-infiltrating characterizations. We comprehensively assessed the prognostic implications of the TLS heterogeneity in 395 patients with ccRCC from multiple cohorts. We then comprehensively assessed the implications for prognosis and immune responses of the TLS spatial and maturation heterogeneity in 355 ccRCC patients and spatial transcriptomic sequencing in 10 non-ccRCC.
Results
A higher proportion of early TLS was found in peritumoral TLS, while intratumoral TLS mainly comprised secondary follicle-like TLS (SFL-TLS), indicating markedly better survival. Notably, presence of TLS, especially intratumoral TLS and SFL-TLS significantly correlated with better survival and objective reflection rate for ccRCC patients receiving anti-PD-1/PD-L1 immunotherapies. In peritumoral TLS cluster, primary follicle-like TLS, the proportion of tumor-associated macrophages and Treg infiltration in the peritumoral regions increased prominently, suggesting an immunosuppressive tumor microenvironment. Interestingly, spatial transcriptome annotation and multispectral fluorescent showed that an abundance of mature plasma cells within mature TLS has the capacity to produce IgA and IgG, which demonstrate significantly higher objective response rates and superior prognosis for ccRCC patients subjected to immunotherapy.
Conclusions
In conclusion, this study revealed the predictive value of TLS heterogeneity in maturation status and localization on the progression and immunological responses of ccRCC for the first time. The morphology of most TLS reside in the peritumoral area tends to exhibit lower maturity. These findings would allow the identification of immunophenotypes and the improvement of immunotherapeutic effectiveness for ccRCC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Ethics committee of Fudan University Shanghai Cancer Center (No: 050432-4-2108*, FUSCC, Shanghai, China).
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.