1.Clinical characteristics of locally advanced rectal cancer patients with pathological complete response after neoadjuvant chemoradiotherapy combined with immunotherapy: a national multicenter study
Jiale GAO ; Yuanyuan2 YANG ; Zhengyang YANG ; Jiagang3 HAN ; Ang? LI ; Gang? LIU ; Yi? SUN ; Liting SUN ; Pengyu WEI ; Jianyong ZHENG ; Hongwei YAO ; Zhongtao ZHANG
Chinese Journal of Digestive Surgery 2025;24(6):739-745
Objective:To analyze the clinical characteristics of locally advanced rectal cancer patients with pathological complete response (pCR) after neoadjuvant chemoradiotherapy combined with immunotherapy.Methods:The retrospective cohort study was conducted. The clinicopatholo-gical data of 46 patients with locally advanced rectal cancer who were admitted to 6 medical centers, including Beijing Friendship Hospital of Capital Medical University et al, from June 2021 to November 2022 were collected. There were 29 males and 17 females, aged (61±4)years. Patients received neoadjuvant chemoradiotherapy combined with immune checkpoint inhibitor therapy, and under-went radical total mesorectal excision during 6-12 weeks after radiotherapy. Observation indicators: (1) comparison of clinical characteristics between pCR and non-pCR patients;(2) postoperative complications and adverse reactions of pCR and non-pCR patients. Comparison of measurement data with normal distribution between groups was conducted using the t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. Results:(1) Comparison of clinical characteristics between pCR and non-pCR patients. Before neoadjuvant therapy, there were 14 cases aged ≥50 years and 6 cases aged <50 years in pCR patients, versus 25 cases and 1 case in non-pCR patients, showing a significant difference between the two groups ( P<0.05). After neoadjuvant therapy, cases in clinical stage T0, T1, T2, T3, T4 were 11, 1, 5, 3, 0 for pCR patients versus 7, 4, 2, 11, 2 for non-pCR patients, cases of tumor regression grade 1, 2, 3, 4 were 11, 8, 1, 0 for pCR patients versus 7, 14, 4, 1 for non-pCR patients, cases in low-risk, medium-risk, high-risk of neoadjuvant rectal scoring and grading were 20, 0, 0 for pCR patients versus 4, 18, 4 for non-pCR patients, respectively, showing significant differences in above indicators between the two groups ( Z=-2.256, -2.104, -5.458, P<0.05). (2) Postoperative complications and adverse reactions of pCR and non-pCR patients. Postoperative complications occurred in 2 cases of pCR patients and 5 cases of non-pCR patients, postoperative adverse reactions occurred in 11 cases of pCR patients and 10 cases of non-pCR patients, showing no significant difference between the two groups ( P>0.05). Conclusion:Compared with locally advanced rectal cancer patients aged ≥50 years, those aged <50 years have significant benefits from neoadjuvant chemoradiotherapy combined with immunotherapy. Clinical T staging and magnetic resonance imaging-detected tumor regression grade after neoadjuvant therapy have predictive value for patients with pCR .
2.Clinical characteristics of locally advanced rectal cancer patients with pathological complete response after neoadjuvant chemoradiotherapy combined with immunotherapy: a national multicenter study
Jiale GAO ; Yuanyuan2 YANG ; Zhengyang YANG ; Jiagang3 HAN ; Ang? LI ; Gang? LIU ; Yi? SUN ; Liting SUN ; Pengyu WEI ; Jianyong ZHENG ; Hongwei YAO ; Zhongtao ZHANG
Chinese Journal of Digestive Surgery 2025;24(6):739-745
Objective:To analyze the clinical characteristics of locally advanced rectal cancer patients with pathological complete response (pCR) after neoadjuvant chemoradiotherapy combined with immunotherapy.Methods:The retrospective cohort study was conducted. The clinicopatholo-gical data of 46 patients with locally advanced rectal cancer who were admitted to 6 medical centers, including Beijing Friendship Hospital of Capital Medical University et al, from June 2021 to November 2022 were collected. There were 29 males and 17 females, aged (61±4)years. Patients received neoadjuvant chemoradiotherapy combined with immune checkpoint inhibitor therapy, and under-went radical total mesorectal excision during 6-12 weeks after radiotherapy. Observation indicators: (1) comparison of clinical characteristics between pCR and non-pCR patients;(2) postoperative complications and adverse reactions of pCR and non-pCR patients. Comparison of measurement data with normal distribution between groups was conducted using the t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. Results:(1) Comparison of clinical characteristics between pCR and non-pCR patients. Before neoadjuvant therapy, there were 14 cases aged ≥50 years and 6 cases aged <50 years in pCR patients, versus 25 cases and 1 case in non-pCR patients, showing a significant difference between the two groups ( P<0.05). After neoadjuvant therapy, cases in clinical stage T0, T1, T2, T3, T4 were 11, 1, 5, 3, 0 for pCR patients versus 7, 4, 2, 11, 2 for non-pCR patients, cases of tumor regression grade 1, 2, 3, 4 were 11, 8, 1, 0 for pCR patients versus 7, 14, 4, 1 for non-pCR patients, cases in low-risk, medium-risk, high-risk of neoadjuvant rectal scoring and grading were 20, 0, 0 for pCR patients versus 4, 18, 4 for non-pCR patients, respectively, showing significant differences in above indicators between the two groups ( Z=-2.256, -2.104, -5.458, P<0.05). (2) Postoperative complications and adverse reactions of pCR and non-pCR patients. Postoperative complications occurred in 2 cases of pCR patients and 5 cases of non-pCR patients, postoperative adverse reactions occurred in 11 cases of pCR patients and 10 cases of non-pCR patients, showing no significant difference between the two groups ( P>0.05). Conclusion:Compared with locally advanced rectal cancer patients aged ≥50 years, those aged <50 years have significant benefits from neoadjuvant chemoradiotherapy combined with immunotherapy. Clinical T staging and magnetic resonance imaging-detected tumor regression grade after neoadjuvant therapy have predictive value for patients with pCR .
3.Tumor-associated neutrophils in EBV-positive nasopharyngeal carcinoma suppress the activation of CD8+ T cells in tumor microenvironment
OUYANG Dijun1 ; CHEN Nan1 ; YANG Jieying2 ; CHEN Yuanyuan2 ; XIANG Tong2,▲ ; XIA Jianchuan2
Chinese Journal of Cancer Biotherapy 2022;29(5):399-409
[Abstract] Objective: To analyze tumor-associated neutrophils (TANs) infiltration in EBV-positive nasopharyngeal carcinoma (NPC) tumor microenvironment (TME) and its correlation with the prognosis and clinicopathological features of patients with NPC, and to preliminarily investigate the role of TANs in activating CD8+ T cells in EBV-positive NPC. Methods: Tumor tissue specimens from 118 patients with EBV-positive NPC without metastases admitted to Sun Yat-sen University Cancer Center from 2008 to 2012 were collected. Immunohistochemistry was performed to analyze CD8+ T cells infiltration and TANs infiltration in NPC and their correlation with EBV infection, and to evaluate the infiltration of TANs in 118 human EBV-positive NPC tissue samples and analyze its correlation with the prognosis and clinicopathological features of NPC patients; flow cytometry was used to detect the expression of N2 marker (CD182 and CD206) of neutrophils stimulated by HK1-EBV-conditioned medium and the expression of CD69 and PD-1 of CD8+ T cells co-cultured with TANs. Results: There were more CD8+ T cells and neutrophils infiltrating in EBV-positive NPC where they were negatively correlated(P=0.0052); densely infiltrated TANs in EBV-positive NPC tissues were positively correlated with poor prognosis of patients (P=0.025 in OS; P=0.027 in PFS); the infiltration of TANs was proved to be an independent risk factor for overall survival (P=0.035) in patients with NPC; compared with Control group, freshly isolated neutrophils cultured in HK1-EBV-conditioned medium showed an increased expression of N2 markers (P<0.001 in CD182; P<0.01 in CD206) which could suppress the expression of CD69 and promote the expression of PD-1 of CD8+ T cells. Conclusion: More TANs infiltrate in EBV-positive NPC where they polarize into N2 neutrophils, exerting an immunosuppressive effect by suppressing the activation of CD8+ T cells and having a positive correlation with the poor prognosis of NPC patients.

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