ESTRO 2024 - Abstract Book

S435

Clinical - Biomarkers

ESTRO 2024

92

Digital Poster

Plasma cells derived from mature tertiary lymphoid structures predict the efficacy of PD-1 blockade

You-Xin Gao 1 , Yin-Hua Ye 1 , Chen-Yang Jiang 2

1 Fujian Medical University Union Hospital, Department of Gastric Surgery, Fuzhou, China. 2 Fujian Medical University Union Hospital, Department of Gastric Surgery,, Fuzhou, China

Purpose/Objective:

The efficacy of neoadjuvant immune checkpoint inhibitor therapy has been demonstrated in clinical trials. The presence of intratumoral tertiary lymphoid structures (TLS) is significantly associated with favorable response to immune checkpoint inhibitors. However, the size of gastroscopic biopsy samples limits the detection rate of TLS in gastric cancer, and it is difficult to identify patients with advanced gastric cancer who are suitable for neoadjuvant immune checkpoint inhibitor therapy.

Material/Methods:

Here, we explored the correlation between TLS and clinical features using tumor tissue sections from 950 patients with advanced gastric cancer from seven centers in China. Subsequently, we recruited 32 patients with advanced gastric cancer who had not received any preoperative drug therapy and performed single-cell and spatial transcriptome sequencing to investigate the tumor microenvironment of mature TLS patients by RCTD. The BCR analysis and multiplex fluorescence immunohistochemical B cells were used to study the B cell responses in mature TLS to find effective biomarkers of mature TLS, and to verify the representative of this marker for mature TLS in tumor tissue sections of multi-center advanced gastric cancer patients. The efficacy of this marker was further validated by establishing an immunotherapy cohort including 25 patients treated with programmed cell death 1 blockade using gastroscopic tumor tissue sections.

Results:

The prognosis of gastric cancer patients with mature TLS was significantly better than those with immature TLS and no TLS. Mature TLS was an independent protective factor for the prognosis of patients with advanced gastric cancer. Single cell joint spatial transcriptome analysis showed that all types of B cells were significantly enriched in the mature TLS, and each stage of B cell differentiation into plasma cells could be identified. In mature TLS, B cells undergo clonal selection and high frequency mutations, and mature B cell clonal subtypes can also be detected in the surrounding tumor area. Plasma cells in mature TLS can migrate long distances in tumors under the guidance of fibroblasts. In our immunotherapy cohort, we found that the treatment response and progression-free survival of gastric cancer patients who received neoadjuvant immune checkpoint inhibitor therapy were closely related to plasma cell content.

Conclusion:

We comprehensively analyzed B cells in the mature TLS of GC. The spatial transcriptomics demonstrated that the mature TLS is the site of B cell maturation, clonal selection, and clonal expansion.