Tumor-Infiltrating Cytotoxic T Cells and Tumor-Associated Macrophages Correlate With the Outcomes of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer
BackgroundTumor-infiltrating immune cells (TIICs) play a key role in immunoregulatory networks and are related to tumor development. Emerging evidence shows that these cells are associated with sensitivity to chemotherapy and radiotherapy. However, the predictive role of TIICs in the outcomes of neo...
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.743540/full |
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| author | Yuqin Yang Yuqin Yang Yuqin Yang Yuqin Yang Wenjing Tian Liqian Su Peiqiu Li Xiaohua Gong Xiaohua Gong Lu Shi Qingling Zhang Qingling Zhang Bin Zhao Hong Zhao Hong Zhao |
| author_facet | Yuqin Yang Yuqin Yang Yuqin Yang Yuqin Yang Wenjing Tian Liqian Su Peiqiu Li Xiaohua Gong Xiaohua Gong Lu Shi Qingling Zhang Qingling Zhang Bin Zhao Hong Zhao Hong Zhao |
| author_sort | Yuqin Yang |
| collection | DOAJ |
| description | BackgroundTumor-infiltrating immune cells (TIICs) play a key role in immunoregulatory networks and are related to tumor development. Emerging evidence shows that these cells are associated with sensitivity to chemotherapy and radiotherapy. However, the predictive role of TIICs in the outcomes of neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC) is unclear.MethodsImaging mass cytometry (IMC) was performed to comprehensively assess the immune status before nCRT in 6 patients with LARC (3 achieved pathological complete response (pCR), 3 did not) with matched clinicopathological parameters. Immunohistochemistry (IHC) for CD8, CD163 and Foxp3 on biopsy samples from 70 patients prior to nCRT and logistic regression analysis were combined to further evaluate its predictive value for treatment responses in an independent validation group.ResultsA trend of increased CD8+ cytotoxic T lymphocytes (CTLs) and decreased CD163+ tumor-associated macrophages (TAMs) and Foxp3+ regulatory T cells (Tregs) in the pCR group was revealed by IMC. In the validation group, CTLs and TAMs were strong predictors of the clinical response to nCRT. High levels of CTLs were positively associated with the pCR ratio (OR=1.042; 95% CI: 1.015~1.070, p=0.002), whereas TAMs were correlated with a poor response (OR=0.969; 95% CI: 0.941~0.998, p=0.036). A high density of TAMs was also associated with an advanced cN stage.ConclusionCTLs in the tumor microenvironment (TME) may improve the response to nCRT, whereas TAMs have the opposite effect. These results suggest that these cells might be potential markers for the clinical outcomes of nCRT and aid in the clinical decision-making of LARC for improved clinical outcomes. |
| first_indexed | 2024-12-20T02:53:03Z |
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| id | doaj.art-b54f4ec0b2e54e0caa59021daab3f113 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-20T02:53:03Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-b54f4ec0b2e54e0caa59021daab3f1132022-12-21T19:55:59ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-10-011110.3389/fonc.2021.743540743540Tumor-Infiltrating Cytotoxic T Cells and Tumor-Associated Macrophages Correlate With the Outcomes of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal CancerYuqin Yang0Yuqin Yang1Yuqin Yang2Yuqin Yang3Wenjing Tian4Liqian Su5Peiqiu Li6Xiaohua Gong7Xiaohua Gong8Lu Shi9Qingling Zhang10Qingling Zhang11Bin Zhao12Hong Zhao13Hong Zhao14The Cancer Center of The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, ChinaDepartment of Pathology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Pathology, School of Basic Medical Science, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, ChinaThe Cancer Center of The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, ChinaPrecision Medicine Center of Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Nephrology, The Fifth Hospital Affifiliated of Sun Yat-sen University, Zhuhai, ChinaThe Cancer Center of The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, ChinaGuangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, ChinaThe Cancer Center of The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, ChinaDepartment of Pathology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Pathology, School of Basic Medical Science, Southern Medical University, Guangzhou, ChinaThe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaThe Cancer Center of The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, ChinaGuangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, ChinaBackgroundTumor-infiltrating immune cells (TIICs) play a key role in immunoregulatory networks and are related to tumor development. Emerging evidence shows that these cells are associated with sensitivity to chemotherapy and radiotherapy. However, the predictive role of TIICs in the outcomes of neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC) is unclear.MethodsImaging mass cytometry (IMC) was performed to comprehensively assess the immune status before nCRT in 6 patients with LARC (3 achieved pathological complete response (pCR), 3 did not) with matched clinicopathological parameters. Immunohistochemistry (IHC) for CD8, CD163 and Foxp3 on biopsy samples from 70 patients prior to nCRT and logistic regression analysis were combined to further evaluate its predictive value for treatment responses in an independent validation group.ResultsA trend of increased CD8+ cytotoxic T lymphocytes (CTLs) and decreased CD163+ tumor-associated macrophages (TAMs) and Foxp3+ regulatory T cells (Tregs) in the pCR group was revealed by IMC. In the validation group, CTLs and TAMs were strong predictors of the clinical response to nCRT. High levels of CTLs were positively associated with the pCR ratio (OR=1.042; 95% CI: 1.015~1.070, p=0.002), whereas TAMs were correlated with a poor response (OR=0.969; 95% CI: 0.941~0.998, p=0.036). A high density of TAMs was also associated with an advanced cN stage.ConclusionCTLs in the tumor microenvironment (TME) may improve the response to nCRT, whereas TAMs have the opposite effect. These results suggest that these cells might be potential markers for the clinical outcomes of nCRT and aid in the clinical decision-making of LARC for improved clinical outcomes.https://www.frontiersin.org/articles/10.3389/fonc.2021.743540/fullcytotoxic T lymphocytestumor-associated macrophagesrectal cancerneoadjuvant chemoradiotherapypathological complete response |
| spellingShingle | Yuqin Yang Yuqin Yang Yuqin Yang Yuqin Yang Wenjing Tian Liqian Su Peiqiu Li Xiaohua Gong Xiaohua Gong Lu Shi Qingling Zhang Qingling Zhang Bin Zhao Hong Zhao Hong Zhao Tumor-Infiltrating Cytotoxic T Cells and Tumor-Associated Macrophages Correlate With the Outcomes of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer Frontiers in Oncology cytotoxic T lymphocytes tumor-associated macrophages rectal cancer neoadjuvant chemoradiotherapy pathological complete response |
| title | Tumor-Infiltrating Cytotoxic T Cells and Tumor-Associated Macrophages Correlate With the Outcomes of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer |
| title_full | Tumor-Infiltrating Cytotoxic T Cells and Tumor-Associated Macrophages Correlate With the Outcomes of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer |
| title_fullStr | Tumor-Infiltrating Cytotoxic T Cells and Tumor-Associated Macrophages Correlate With the Outcomes of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer |
| title_full_unstemmed | Tumor-Infiltrating Cytotoxic T Cells and Tumor-Associated Macrophages Correlate With the Outcomes of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer |
| title_short | Tumor-Infiltrating Cytotoxic T Cells and Tumor-Associated Macrophages Correlate With the Outcomes of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer |
| title_sort | tumor infiltrating cytotoxic t cells and tumor associated macrophages correlate with the outcomes of neoadjuvant chemoradiotherapy for locally advanced rectal cancer |
| topic | cytotoxic T lymphocytes tumor-associated macrophages rectal cancer neoadjuvant chemoradiotherapy pathological complete response |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.743540/full |
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