Abstract
BackgroundWith the interest in cancer immunotherapy, it may be possible to combine immunotherapy with bevacizumab and chemotherapy. We evaluated whether tumor-infiltrating immune cells are associated with the efficacy of chemotherapy with or without bevacizumab for the treatment of metastatic colorectal cancer (mCRC).MethodsThis study enrolled mCRC patients on standard treatment with available detailed data and tumor tissue at Sun Yat-sen University Cancer Center between July 1, 2005, and October 1, 2017. CD3+ and CD8+ T cell densities examined by immunohistochemistry in both the tumor core (CT) and invasive margin (IM) were summed as the Immunoscore, and the CD8+/CD3+ T cell ratio was calculated. The predictive and prognostic efficacies of tumor-infiltrating immune cells for progression-free survival (PFS) and overall survival (OS) were analyzed with Kaplan-Meier and Cox analyses.ResultsThe CD8+/CD3+ T cell ratio in the microenvironment was an independent prognostic factor for OS (28.12 mo vs. 16.56 mo, P = 0.017) among the 108 studied patients. In the chemotherapy only group, patients with a high Immunoscore had a high overall response rate (ORR, 40.0% vs. 60.0%, P = 0.022), those with a low CD8+/CD3+ T cell ratio in the microenvironment had a significantly longer PFS (8.64 mo vs. 6.01 mo, P = 0.017), and those with a high CD3+ T cell density in the CT had a longer OS (16.56 mo vs. 25.66 mo, P = 0.029). In the chemotherapy combined with bevacizumab group, patients with a higher CD8+ T cell density in the IM had a longer PFS (7.62 mo vs. 11.66 mo, P = 0.034) and OS (14.55 mo vs. 23.72 mo, P = 0.033).ConclusionImmune cells in primary tumors play an important role in predicting mCRC treatment efficacy. CD8 predicts the effect of bevacizumab plus chemotherapy, while CD3 and CD8/CD3 predict chemotherapy efficacy.
Highlights
Colorectal cancer (CRC) is the third most common cancer in the world
In the chemotherapy combined with bevacizumab group, patients with a higher percentage of CD8+ T cells in the invasive margin (IM) had a longer progression-free survival (PFS) and overall survival (OS)
The present study found that N stage and synchronous/ metachronous metastasis were associated with immune cell concentrations in metastatic colorectal cancer (mCRC)
Summary
Colorectal cancer (CRC) is the third most common cancer in the world. Metastases are present in approximately 25% to 30% of patients at diagnosis and develop in up to 50% of patients thereafter [1]. There has been increasing attention has been paid to predicting CRC prognosis with a focus on tumor cells, mutation status, molecular pathways and immune cell infiltration [6]. The host immune response has been found to play an important role in determining the outcome of patients with CRC. It has been suggested that the analysis of immune cells in the microenvironment in combination with the AJCC/UICC stage could lead to a better determination of patient prognosis [13]. We investigated CD3+ (total) and CD8+ (cytotoxic) T cells to determine the prognosis of mCRC patients on standard palliative treatment. We evaluated whether tumorinfiltrating immune cells are associated with the efficacy of chemotherapy with or without bevacizumab for the treatment of metastatic colorectal cancer (mCRC)
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