Tumor Microenvironment before and after Chemoradiation in Locally Advanced Rectal Cancer: Beyond PD-L1
Background: In locally advanced rectal cancer treatment, neoadjuvant concurrent chemoradiation therapy (cCRT) is the standard of care. The tumor microenvironment (TME) is a complex entity comprising of tumor cells, immune cells and surrounding stroma and is closely associated with tumor growth and s...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/1/276 |
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| author | Pritam Tayshetye Andrew J. Friday Ashten N. Omstead Tanvi Verma Stacey Miller Ping Zheng Prashant Jani Ali Zaidi Gene Finley |
| author_facet | Pritam Tayshetye Andrew J. Friday Ashten N. Omstead Tanvi Verma Stacey Miller Ping Zheng Prashant Jani Ali Zaidi Gene Finley |
| author_sort | Pritam Tayshetye |
| collection | DOAJ |
| description | Background: In locally advanced rectal cancer treatment, neoadjuvant concurrent chemoradiation therapy (cCRT) is the standard of care. The tumor microenvironment (TME) is a complex entity comprising of tumor cells, immune cells and surrounding stroma and is closely associated with tumor growth and survival, response to antitumor therapies and also resistance to treatment. We aimed to assess the change in biomarkers associated with TME following standard neoadjuvant cCRT in rectal cancer. Methods: We accessed archival tissue from rectal cancer patients treated with neoadjuvant cCRT at Allegheny Health Network (AHN) facilities over the past 14 years. Pre-treatment and post-treatment biopsies were assayed for PD-L1, CD8+ T-cells, CXCL9, TIM-3, IDO-1, IFN-G, IL17RE, LAG-3, and OX40 in 41 patients. Results: We found statistically significant upregulation in multiple biomarkers namely CD8, IL17RE, LAG3 and OX40 post neoadjuvant cCRT and a trend towards upregulation, although not statistically significant, in biomarkers PD-L1, CXCL9, TIM-3, IDO-1 and IFN-G expression. Conclusions: This provides a glimpse into the TME before and after neoadjuvant cCRT. We suggest that the biomarkers noted to be upregulated could be used for designing appropriate clinical trials and development of therapeutic targeted drug therapy in an effort to achieve better response to neoadjuvant therapy, increasing clinical and pathological complete response rates and improved overall outcomes. |
| first_indexed | 2024-03-11T10:06:17Z |
| format | Article |
| id | doaj.art-cada4eac80c44ed1bace78bfc7cba264 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T10:06:17Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-cada4eac80c44ed1bace78bfc7cba2642023-11-16T15:04:01ZengMDPI AGCancers2072-66942022-12-0115127610.3390/cancers15010276Tumor Microenvironment before and after Chemoradiation in Locally Advanced Rectal Cancer: Beyond PD-L1Pritam Tayshetye0Andrew J. Friday1Ashten N. Omstead2Tanvi Verma3Stacey Miller4Ping Zheng5Prashant Jani6Ali Zaidi7Gene Finley8Department of Hematology-Oncology, Allegheny Health Network, Pittsburgh, PA 15212, USADepartment of Medical Oncology, Allegheny General Hospital, Pittsburgh, PA 15212, USAEsophageal and Lung Institute, Allegheny Health Network, Pittsburgh, PA 15212, USADepartment of Pathology and Laboratory Medicine, Allegheny Health Network, Pittsburgh, PA 15212, USADepartment of Pathology and Laboratory Medicine, Allegheny Health Network, Pittsburgh, PA 15212, USAEsophageal and Lung Institute, Allegheny Health Network, Pittsburgh, PA 15212, USAHematology and Oncology, Northeast Cancer Centre, Sudbury, ON P3E 5J1, CanadaEsophageal and Lung Institute, Allegheny Health Network, Pittsburgh, PA 15212, USADepartment of Medical Oncology, Allegheny General Hospital, Pittsburgh, PA 15212, USABackground: In locally advanced rectal cancer treatment, neoadjuvant concurrent chemoradiation therapy (cCRT) is the standard of care. The tumor microenvironment (TME) is a complex entity comprising of tumor cells, immune cells and surrounding stroma and is closely associated with tumor growth and survival, response to antitumor therapies and also resistance to treatment. We aimed to assess the change in biomarkers associated with TME following standard neoadjuvant cCRT in rectal cancer. Methods: We accessed archival tissue from rectal cancer patients treated with neoadjuvant cCRT at Allegheny Health Network (AHN) facilities over the past 14 years. Pre-treatment and post-treatment biopsies were assayed for PD-L1, CD8+ T-cells, CXCL9, TIM-3, IDO-1, IFN-G, IL17RE, LAG-3, and OX40 in 41 patients. Results: We found statistically significant upregulation in multiple biomarkers namely CD8, IL17RE, LAG3 and OX40 post neoadjuvant cCRT and a trend towards upregulation, although not statistically significant, in biomarkers PD-L1, CXCL9, TIM-3, IDO-1 and IFN-G expression. Conclusions: This provides a glimpse into the TME before and after neoadjuvant cCRT. We suggest that the biomarkers noted to be upregulated could be used for designing appropriate clinical trials and development of therapeutic targeted drug therapy in an effort to achieve better response to neoadjuvant therapy, increasing clinical and pathological complete response rates and improved overall outcomes.https://www.mdpi.com/2072-6694/15/1/276rectal cancerchemoradiationtumor microenvironmentneoadjuvantbiomarkerimmunotherapy |
| spellingShingle | Pritam Tayshetye Andrew J. Friday Ashten N. Omstead Tanvi Verma Stacey Miller Ping Zheng Prashant Jani Ali Zaidi Gene Finley Tumor Microenvironment before and after Chemoradiation in Locally Advanced Rectal Cancer: Beyond PD-L1 Cancers rectal cancer chemoradiation tumor microenvironment neoadjuvant biomarker immunotherapy |
| title | Tumor Microenvironment before and after Chemoradiation in Locally Advanced Rectal Cancer: Beyond PD-L1 |
| title_full | Tumor Microenvironment before and after Chemoradiation in Locally Advanced Rectal Cancer: Beyond PD-L1 |
| title_fullStr | Tumor Microenvironment before and after Chemoradiation in Locally Advanced Rectal Cancer: Beyond PD-L1 |
| title_full_unstemmed | Tumor Microenvironment before and after Chemoradiation in Locally Advanced Rectal Cancer: Beyond PD-L1 |
| title_short | Tumor Microenvironment before and after Chemoradiation in Locally Advanced Rectal Cancer: Beyond PD-L1 |
| title_sort | tumor microenvironment before and after chemoradiation in locally advanced rectal cancer beyond pd l1 |
| topic | rectal cancer chemoradiation tumor microenvironment neoadjuvant biomarker immunotherapy |
| url | https://www.mdpi.com/2072-6694/15/1/276 |
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