Preoperative Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and CEA as the Potential Prognostic Biomarkers for Colorectal Cancer.

Background: This study was to evaluate the prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and carcinoembryonic antigen (CEA) in colorectal cancer (CRC) patients and to identify the potential and easily accessible prognostic biomarkers for CRC. Methods: We retrospectively reviewed altogether the records of 330 CRC patients according to inclusion criteria. The clinical characteristics include age at diagnosis, body mass index (BMI), preoperative CEA level, neutrophil , lymphocyte, and platelet count, tumor primary site and size, clinical pathological TNM stage, and survival status were recorded through the review of medical records. The overall survival (OS) was calculated using the Kaplan-Meier method. The Cox proportional hazards model was used for the univariate and multivariate analysis to evaluate the prognostic factors of CRC. Results: A total of 330 patients were finally included in the current study. The mean follow-up duration was 32.8 ± 19.1 months (range, 0.1-67.7). Compared with the median OS, preoperative high NLR, PLR, and CEA, and low BMI had lower median OS. The NLR and PLR value rise indicates lower median OS in stage I-II CRC; however, the NLR value and CEA level rise indicates lower median OS in stage III-IV CRC. Preoperative high NLR, PLR, and CEA level and low BMI have poorer OS by univariate analysis. By multivariate analysis, the age, sex, N, M stage, and BMI demonstrated independently influence the OS of CRC. NLR was an independent predictor of stage I-II CRC, and the CEA level was an independent predictor of stage III-IV CRC. Conclusions: Our results show that preoperative high NLR, PLR, CEA, and low BMI had poorer OS, NLR was an independent predictor of stage I-II CRC, and the CEA level was an independent predictor of stage III-IV CRC.

Efficacy and peripheral immunity analysis of allogeneic natural killer cells therapy in patients with hepatocellular carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the safety and efficacy of allogeneic natural killer (NK) cells in the treatment of primary hepatocellular carcinoma (HCC), and to elucidate the mechanism of NK cells therapy.@*METHODS@#Twenty-one patients with primary HCC treated with allogeneic NK cells at the Fifth Medical Center of the PLA General Hospital were followed up for 1 year. Peripheral blood mononuclear cells (PBMCs) were isolated from patient-related donors and cultured in vitro for 15 days and infused to the patients in two consecutive days. Clinical data and laboratory data were collected and analyzed, including survival, clinical features, imaging changes, hematology, immunology, and biochemical indicators to evaluate the safety and efficacy of allogeneic NK cell therapy. The changes of peripheral blood lymphocyte subsets after treatment were also analyzed to explore the possible anti-tumor mechanisms.@*RESULTS@#(1) Of the 21 patients with primary HCC, 11 patients were treated once, 5 patients were treated twice, and 5 patients were treated 3 times. After allogeneic NK cells infusion, 10 patients had fever, 1 patient had slight hepatalgia and 1 patient had slight headache, no other adverse events occurred including acute and chronic graft-versus-host disease (GVHD). They resolved spontaneously within 8 hours without other treatment. (2) The total disease control rate was 76.2% during one-year follow-up. Among them, the patients with Barcelona clinic liver cancer (BCLC) stage A had a disease control rate of 100%, stable disease (SD) in 10 cases; BCLC stage B patients had a disease control rate of 60%, partial response (PR) in 1 case, and SD 2 in cases; BCLC stage C patients had a disease control rate of 50%, complete response (CR) in 1 case, and 2 cases of PR. (3) The frequencies of NK cells and CD8+ T cells in peripheral blood were significantly lower than that before at 24 hours after treatment, and the frequencies of CD4+ T cells and CD4/CD8 were significantly higher than the baseline.@*CONCLUSION@#Allogeneic NK cells have good safety and efficacy in the treatment of primary HCC. The anti-tumor effect of the allogeneic NK cells may play an important role in the activation of the patient's natural immune system and delay disease progression, suggesting that allogeneic NK cells combined with sorafenib may be a very effective treatment for advanced HCC, and further large-sample multicenter randomized controlled clinical trials are needed to validate this result.