Frontiers in Immunology (Mar 2024)

Intratumor tertiary lymphatic structure evaluation predicts the prognosis and immunotherapy response of patients with colorectal cancer

  • Huijing Feng,
  • Siyuan Zhang,
  • Siyuan Zhang,
  • Siyuan Zhang,
  • Siyuan Zhang,
  • Siyuan Zhang,
  • Qiuru Zhou,
  • Qiuru Zhou,
  • Qiuru Zhou,
  • Qiuru Zhou,
  • Qiuru Zhou,
  • Qiuru Zhou,
  • Fei Han,
  • Gang Du,
  • Lin Wang,
  • Xuena Yang,
  • Xuena Yang,
  • Xuena Yang,
  • Xuena Yang,
  • Xuena Yang,
  • Xiying Zhang,
  • Xiying Zhang,
  • Xiying Zhang,
  • Xiying Zhang,
  • Xiying Zhang,
  • Wenwen Yu,
  • Wenwen Yu,
  • Wenwen Yu,
  • Wenwen Yu,
  • Wenwen Yu,
  • Feng Wei,
  • Feng Wei,
  • Feng Wei,
  • Feng Wei,
  • Feng Wei,
  • Feng Wei,
  • Xishan Hao,
  • Xishan Hao,
  • Xishan Hao,
  • Xishan Hao,
  • Xishan Hao,
  • Xiubao Ren,
  • Xiubao Ren,
  • Xiubao Ren,
  • Xiubao Ren,
  • Xiubao Ren,
  • Xiubao Ren,
  • Xiubao Ren,
  • Hua Zhao,
  • Hua Zhao,
  • Hua Zhao,
  • Hua Zhao,
  • Hua Zhao,
  • Hua Zhao

DOI
https://doi.org/10.3389/fimmu.2024.1302903
Journal volume & issue
Vol. 15

Abstract

Read online

BackgroundImmune checkpoint therapy, involving the programmed cell death 1 (PD-1) monoclonal antibody, has revolutionized the treatment of cancer. Tertiary lymphatic structure (TLS) serves as an immune indicator to predict the efficacy of PD-1 antibody therapy. However, there is no clear result whether the distribution, quantity, and maturity of TLS can be effective indicators for predicting the clinical efficacy of anti-PD1 immunotherapy in patients with colorectal cancer (CRC).MethodsFifty-seven patients who underwent surgical resection and thirty-nine patients who received anti-PD-1 immunotherapy were enrolled in this retrospective study. Immunohistochemical staining and multiple fluorescence immunohistochemistry were used to evaluate the mismatch repair (MMR) subtypes and TLS distribution, quantity, and maturity, respectively.ResultsA comprehensive patient score system was built based on TLS quantity and maturity. We found that the proportion of patients with score >1 was much higher in the deficient mismatch repair(dMMR) group than in the proficient mismatch repair(pMMR) group, and this difference was mainly due to intratumoral TLS. Patient score, based on the TLS evaluation of whole tumor, peritumor, or intratumor, was used to evaluate the efficacy of anti-PD1 immunotherapy. Based only on the intratumor TLS evaluation, the proportion of patients with a score >1 was higher in the response (PR + CR) group than in the non-response (PD) group. Multivariate analysis revealed that patient scores were positively correlated with the clinical efficacy of immunotherapy. Further analysis of immune-related progression-free survival was performed in patients with CRC who received anti-PD-1 immunotherapy. Patients with score >1 based on the intratumor TLS evaluation had significantly better survival.ConclusionsThese results suggest that the patient score based on intratumor TLS evaluation may be a good immune predictive indicator for PD-1 antibody therapy in patients with CRC.

Keywords