99P - Extended lymphadenectomy may not be necessary for MSI-H colon cancer patients after immunotherapy

Background

In the era of immunotherapy, whether removal of tumor -draining lymph nodes (TDLNs) should be removed as the traditional surgery way or should be surgical method or preserved preservation remains controversialis still unknown.

Methods

In this study, 42 mismatch repair deficient (dMMR) and 42 mismatch repairs proficient (pMMR) colon cancer patients were enrolled. Imaging data and single-cell RNA sequencing of tumor-draining lymph nodes were also investigated for comprehensive profiling of the microenvironment. The cells of tumor-draining lymph nodes in patients with dMMR colon cancer after neoadjuvant immunotherapy were analyzed to determine their T-cell phenotype.

Results

No significant differences in presurgical clinical characteristics were detected between the dMMR and pMMR groups. However, greater disease-free survival was observed in dMMR patients than in pMMR patients (p =0.02). Approximately 52.4% of patients with dMMR treated with a whole regimen of Pd-1 blockade (dMMR+Pd-1) achieved a pathological complete response (pCR). Eight of the 42 dMMR patients experienced bowel obstruction during treatment. The single-cell transcriptome revealed enrichment of naïve-like CD8+ T cells in the TDLNs of dMMR responders. In addition, we observed that macrophages in dMMR responder TDLNs were polarized toward the M1 phenotype. The altered microenvironment was accompanied by the complete eradication of malignant cells in TDLNs upon Pd-1 blockade treatment.

Conclusions

To maintain a durable response to ICIs, TDLN preservation could be considered a potential reservoir of memory T cells to sustain ICI responses and reduce the risk of relapse and progression in dMMR+Pd-1 blockade colon cancer patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Sun Yat-sen University Cancer Center.

Funding

Sun Yat-sen University Cancer Center, Chinese Society of Clinical Oncology.

Disclosure

All authors have declared no conflicts of interest.