204. CORRELATION OF CIRCULATING T LYMPHOCYTES WITH RESPONSE TO NEOADJUVANT CHEMOIMMUNOTHERAPY IN OPERABLE ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Kunzhi Li, Yixuan Huang, Mu Yang, Kangning Wang, Xing Wei, Qiang Zhou, Yongtao Han, Yan Miao, Qiang Fang- Gastroenterology
- General Medicine
Abstract
Background
There is growing evidence indicating that neoadjuvant chemotherapy combined immune-oncology therapy (neoCTIO) with anti-PD-1 antibodies is effective in esophageal squamous cell carcinoma (ESCC). However, the precise benefits remain unclear. This study aimed to explore whether the subsets and production of effector cytokines in circulating T lymphocytes were correlated with response to neoCTIO with toripalimab in operable ESCC.
Methods
ESCC patients staged cT2N1–2 M0 or cT3–4aN0-2 M0, with ECOG PS 0–1 status randomly received two cycles of different sequences of toripalimab plus chemotherapy (paclitaxel and carboplatin) on day 1 to 2 of each 21-day cycle. Minimally invasive esophagectomy (MIE) was performed 4–8 weeks after neoCTIO. Peripheral blood was collected before and after neoCTIO. Flow cytometry was used to detect the effector cytokines and subsets of CD8+ and CD4+ T lymphocytes. The primary endpoints were the advanced change of subsets, effector cytokines in T lymphocytes, and pathological complete response (pCR). The secondary endpoints included major pathological response (MPR) (NCT05044728).
Results
96.7% (32/33) patients received MIE with R0 resection. 18.8% (6/32) patients achieved pCR and 31.3% (10/32) patients achieved MPR. In the responders, CD8+ T lymphocytes showed higher IFNγ and TNFα coexpression compared to non-responders before neoCTIO (P = 0.010). The responders had higher frequency of effector subsets (P = 0.029) and lower naive subsets (P = 0.006) of CD8+ T lymphocytes than the non-responders before neoCTIO. No difference was found in the cell frequency of CD4+ T lymphocyte subsets between the responders and non-responders. There was no correlation between the change of subsets, effector cytokines in T lymphocytes and the sequence of neoCTIO.
Conclusion
NeoCTIO with toripalimab is effective in the treatment of ESCC. The baseline frequency of effector subsets and coexpression of IFNγ and TNFα in circulating CD8+ T lymphocytes have positive predictive value while the baseline frequency of Naive subsets is a negative biomarker. CD4+ T cell subsets have no correlation with the treatment response. The change of circulating CD8+ T lymphocytes is not affected by the sequence of neoCTIO.