CXCR6+ Tumor-Associated Macrophages Identify Immunosuppressive Colon Cancer Patients with Poor Prognosis but Favorable Response to Adjuvant Chemotherapy
We explored the infiltration and prognostic value of CXCR6+TAMs in all stages of colon cancer (CC) patients and assessed predictive ability as a biomarker for different ACT regimens among high-risk stage II and stage III patients in both primary and validation cohorts. Two independent cohorts of 360...
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| Language: | English |
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MDPI AG
2022-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/19/4646 |
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| author | Jiang Chang Songbin Lin Yihao Mao Yuqiu Xu Zhiyuan Zhang Qi Wu Yijiao Chen Ye Wei Qingyang Feng Jianmin Xu |
| author_facet | Jiang Chang Songbin Lin Yihao Mao Yuqiu Xu Zhiyuan Zhang Qi Wu Yijiao Chen Ye Wei Qingyang Feng Jianmin Xu |
| author_sort | Jiang Chang |
| collection | DOAJ |
| description | We explored the infiltration and prognostic value of CXCR6+TAMs in all stages of colon cancer (CC) patients and assessed predictive ability as a biomarker for different ACT regimens among high-risk stage II and stage III patients in both primary and validation cohorts. Two independent cohorts of 360 and 126 consecutive colon cancer patients were enrolled from two medical centers of Zhongshan Hospital. Immunofluorescence and immunohistochemistry were performed to detect the density of CXCR6+TAMs and activated CD8+ T cells. The infiltration of CXCR6+TAMs was higher in tumor tissues and increased with advanced tumor stage. A high density of CXCR6+TAMs predicted worse overall survival (OS) in all CC patients (HR = 2.49, 95% CI = (1.68, 3.70), <i>p</i> < 0.001), and was an independent risk factor verified by Cox regression analysis (HR = 1.68, 95% CI = (1.09, 2.59), <i>p</i> = 0.019). For high-risk stage II and stage III patients with a high density of CXCR6+TAMs, better disease-free survival (DFS) (HR = 0.32, 95% CI = (0.11, 0.89), <i>p</i> = 0.003), and OS (HR = 0.28, 95% CI = (0.07, 1.11), <i>p</i> = 0.014) were observed in the 6-month treatment group. There was a negative relationship between the density of CXCR6+TAMs and CD8+ T cells (R = −0.51, <i>p</i> < 0.001) as well as activated CD8+ T cells (R = −0.54, <i>p</i> < 0.001). Higher levels of IL-6 and lower levels of IL-2R and TNF-α were expressed in high-CXCR6+ TAM-density patients, which indicates that CXCR6+TAMs contribute to an immunosuppressive microenvironment. CXCR6+TAMs predicted prognosis and response to different durations of ACT in CC patients. CXCR6+TAMs were associated with an immunosuppressive microenvironment and suppressed the activation of CD8+ T cells. |
| first_indexed | 2024-03-09T21:58:02Z |
| format | Article |
| id | doaj.art-ca54821c47ca4fdd93c7ccf36c3a4dac |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T21:58:02Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-ca54821c47ca4fdd93c7ccf36c3a4dac2023-11-23T19:54:15ZengMDPI AGCancers2072-66942022-09-011419464610.3390/cancers14194646CXCR6+ Tumor-Associated Macrophages Identify Immunosuppressive Colon Cancer Patients with Poor Prognosis but Favorable Response to Adjuvant ChemotherapyJiang Chang0Songbin Lin1Yihao Mao2Yuqiu Xu3Zhiyuan Zhang4Qi Wu5Yijiao Chen6Ye Wei7Qingyang Feng8Jianmin Xu9Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200000, ChinaGeneral Surgery Department, Zhongshan Hospital, Fudan University (Xiamen Branch), Xiamen 361000, ChinaColorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200000, ChinaColorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200000, ChinaColorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200000, ChinaColorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200000, ChinaColorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200000, ChinaColorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200000, ChinaColorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200000, ChinaColorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200000, ChinaWe explored the infiltration and prognostic value of CXCR6+TAMs in all stages of colon cancer (CC) patients and assessed predictive ability as a biomarker for different ACT regimens among high-risk stage II and stage III patients in both primary and validation cohorts. Two independent cohorts of 360 and 126 consecutive colon cancer patients were enrolled from two medical centers of Zhongshan Hospital. Immunofluorescence and immunohistochemistry were performed to detect the density of CXCR6+TAMs and activated CD8+ T cells. The infiltration of CXCR6+TAMs was higher in tumor tissues and increased with advanced tumor stage. A high density of CXCR6+TAMs predicted worse overall survival (OS) in all CC patients (HR = 2.49, 95% CI = (1.68, 3.70), <i>p</i> < 0.001), and was an independent risk factor verified by Cox regression analysis (HR = 1.68, 95% CI = (1.09, 2.59), <i>p</i> = 0.019). For high-risk stage II and stage III patients with a high density of CXCR6+TAMs, better disease-free survival (DFS) (HR = 0.32, 95% CI = (0.11, 0.89), <i>p</i> = 0.003), and OS (HR = 0.28, 95% CI = (0.07, 1.11), <i>p</i> = 0.014) were observed in the 6-month treatment group. There was a negative relationship between the density of CXCR6+TAMs and CD8+ T cells (R = −0.51, <i>p</i> < 0.001) as well as activated CD8+ T cells (R = −0.54, <i>p</i> < 0.001). Higher levels of IL-6 and lower levels of IL-2R and TNF-α were expressed in high-CXCR6+ TAM-density patients, which indicates that CXCR6+TAMs contribute to an immunosuppressive microenvironment. CXCR6+TAMs predicted prognosis and response to different durations of ACT in CC patients. CXCR6+TAMs were associated with an immunosuppressive microenvironment and suppressed the activation of CD8+ T cells.https://www.mdpi.com/2072-6694/14/19/4646tumor-associated macrophagescolon canceradjuvant chemotherapyimmune microenvironment |
| spellingShingle | Jiang Chang Songbin Lin Yihao Mao Yuqiu Xu Zhiyuan Zhang Qi Wu Yijiao Chen Ye Wei Qingyang Feng Jianmin Xu CXCR6+ Tumor-Associated Macrophages Identify Immunosuppressive Colon Cancer Patients with Poor Prognosis but Favorable Response to Adjuvant Chemotherapy Cancers tumor-associated macrophages colon cancer adjuvant chemotherapy immune microenvironment |
| title | CXCR6+ Tumor-Associated Macrophages Identify Immunosuppressive Colon Cancer Patients with Poor Prognosis but Favorable Response to Adjuvant Chemotherapy |
| title_full | CXCR6+ Tumor-Associated Macrophages Identify Immunosuppressive Colon Cancer Patients with Poor Prognosis but Favorable Response to Adjuvant Chemotherapy |
| title_fullStr | CXCR6+ Tumor-Associated Macrophages Identify Immunosuppressive Colon Cancer Patients with Poor Prognosis but Favorable Response to Adjuvant Chemotherapy |
| title_full_unstemmed | CXCR6+ Tumor-Associated Macrophages Identify Immunosuppressive Colon Cancer Patients with Poor Prognosis but Favorable Response to Adjuvant Chemotherapy |
| title_short | CXCR6+ Tumor-Associated Macrophages Identify Immunosuppressive Colon Cancer Patients with Poor Prognosis but Favorable Response to Adjuvant Chemotherapy |
| title_sort | cxcr6 tumor associated macrophages identify immunosuppressive colon cancer patients with poor prognosis but favorable response to adjuvant chemotherapy |
| topic | tumor-associated macrophages colon cancer adjuvant chemotherapy immune microenvironment |
| url | https://www.mdpi.com/2072-6694/14/19/4646 |
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