Prognostic Features and Potential for Immune Therapy in Metastatic Mismatch Repair‐Deficient Colorectal Cancer: A Retrospective Analysis of a Large Consecutive Population‐Based Patient Series
ABSTRACT Background Immune checkpoint inhibition therapies have provided remarkable results in numerous metastatic cancers, including mismatch repair–deficient (dMMR) colorectal cancer (CRC). To evaluate the potential for PD‐1 blockade therapy in a large population‐based cohort, we analyzed the tumo...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Cancer Medicine |
| Online Access: | https://doi.org/10.1002/cam4.70555 |
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| author | Erkki‐Ville Wirta Hanna Elomaa Jukka‐Pekka Mecklin Toni T. Seppälä Marja Hyöty Jan Böhm Maarit Ahtiainen Juha P. Väyrynen |
| author_facet | Erkki‐Ville Wirta Hanna Elomaa Jukka‐Pekka Mecklin Toni T. Seppälä Marja Hyöty Jan Böhm Maarit Ahtiainen Juha P. Väyrynen |
| author_sort | Erkki‐Ville Wirta |
| collection | DOAJ |
| description | ABSTRACT Background Immune checkpoint inhibition therapies have provided remarkable results in numerous metastatic cancers, including mismatch repair–deficient (dMMR) colorectal cancer (CRC). To evaluate the potential for PD‐1 blockade therapy in a large population‐based cohort, we analyzed the tumor microenvironment and reviewed the clinical data and actualized treatment of all dMMR CRCs in Central Finland province between 2000 and 2015. Material and Methods Of 1343 CRC patients, 171 dMMR tumors were identified through immunohistochemical screening. Histological tumor parameters were evaluated from hematoxylin‐ and eosin‐stained whole‐slide samples. CD3 and CD8 immunohistochemistry were analyzed to calculate T‐cell densities in the tumor center and invasive margin, and G‐cross function values to estimate cancer cell–T‐cell co‐localization. Multiplex immunohistochemistry was used to identify CD68+PD‐L1+ and CD3+PD‐1+ immune cells and PD‐L1 expression on tumor cells. Results A total of 35 (20%) patients with dMMR tumors were diagnosed as having a metastatic disease. Twelve patients (34%) were fit enough to be offered oncological treatments at the onset of non‐curable metastatic disease. High proportions of necrosis and stroma were common in metastatic tumors and were associated with worse survival. Crohn's‐like reaction, T‐cell proximity score, and CD68+/PD‐L1+ on the tumor center and invasive margin were independent prognostic immune factors. Conclusion As dMMR CRC patients are generally older, with often significant comorbidities, only a limited portion of patients with metastatic dMMR tumors ended up in oncological treatments. Many of the metastatic tumors presented features that may impair response to PD‐1 blockade therapy. |
| format | Article |
| id | doaj-art-19668bf90f7f4599b5a8aba8045a4da4 |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-19668bf90f7f4599b5a8aba8045a4da42025-01-13T13:22:39ZengWileyCancer Medicine2045-76342025-01-01141n/an/a10.1002/cam4.70555Prognostic Features and Potential for Immune Therapy in Metastatic Mismatch Repair‐Deficient Colorectal Cancer: A Retrospective Analysis of a Large Consecutive Population‐Based Patient SeriesErkki‐Ville Wirta0Hanna Elomaa1Jukka‐Pekka Mecklin2Toni T. Seppälä3Marja Hyöty4Jan Böhm5Maarit Ahtiainen6Juha P. Väyrynen7Department of Gastroenterology and Alimentary Tract Surgery Tampere University Hospital Tampere FinlandDepartment of Biological and Environmental Science University of Jyväskylä Jyväskylä FinlandDepartment of Education and Research The Wellbeing Services of Central Finland Jyväskylä FinlandDepartment of Gastroenterology and Alimentary Tract Surgery Tampere University Hospital Tampere FinlandDepartment of Gastroenterology and Alimentary Tract Surgery Tampere University Hospital Tampere FinlandDepartment of Pathology Wellbeing Services County of Central Finland Jyväskylä FinlandDepartment of Pathology Wellbeing Services County of Central Finland Jyväskylä FinlandTranslational Medicine Research Unit, Medical Research Center Oulu Oulu University Hospital, and University of Oulu Oulu FinlandABSTRACT Background Immune checkpoint inhibition therapies have provided remarkable results in numerous metastatic cancers, including mismatch repair–deficient (dMMR) colorectal cancer (CRC). To evaluate the potential for PD‐1 blockade therapy in a large population‐based cohort, we analyzed the tumor microenvironment and reviewed the clinical data and actualized treatment of all dMMR CRCs in Central Finland province between 2000 and 2015. Material and Methods Of 1343 CRC patients, 171 dMMR tumors were identified through immunohistochemical screening. Histological tumor parameters were evaluated from hematoxylin‐ and eosin‐stained whole‐slide samples. CD3 and CD8 immunohistochemistry were analyzed to calculate T‐cell densities in the tumor center and invasive margin, and G‐cross function values to estimate cancer cell–T‐cell co‐localization. Multiplex immunohistochemistry was used to identify CD68+PD‐L1+ and CD3+PD‐1+ immune cells and PD‐L1 expression on tumor cells. Results A total of 35 (20%) patients with dMMR tumors were diagnosed as having a metastatic disease. Twelve patients (34%) were fit enough to be offered oncological treatments at the onset of non‐curable metastatic disease. High proportions of necrosis and stroma were common in metastatic tumors and were associated with worse survival. Crohn's‐like reaction, T‐cell proximity score, and CD68+/PD‐L1+ on the tumor center and invasive margin were independent prognostic immune factors. Conclusion As dMMR CRC patients are generally older, with often significant comorbidities, only a limited portion of patients with metastatic dMMR tumors ended up in oncological treatments. Many of the metastatic tumors presented features that may impair response to PD‐1 blockade therapy.https://doi.org/10.1002/cam4.70555 |
| spellingShingle | Erkki‐Ville Wirta Hanna Elomaa Jukka‐Pekka Mecklin Toni T. Seppälä Marja Hyöty Jan Böhm Maarit Ahtiainen Juha P. Väyrynen Prognostic Features and Potential for Immune Therapy in Metastatic Mismatch Repair‐Deficient Colorectal Cancer: A Retrospective Analysis of a Large Consecutive Population‐Based Patient Series Cancer Medicine |
| title | Prognostic Features and Potential for Immune Therapy in Metastatic Mismatch Repair‐Deficient Colorectal Cancer: A Retrospective Analysis of a Large Consecutive Population‐Based Patient Series |
| title_full | Prognostic Features and Potential for Immune Therapy in Metastatic Mismatch Repair‐Deficient Colorectal Cancer: A Retrospective Analysis of a Large Consecutive Population‐Based Patient Series |
| title_fullStr | Prognostic Features and Potential for Immune Therapy in Metastatic Mismatch Repair‐Deficient Colorectal Cancer: A Retrospective Analysis of a Large Consecutive Population‐Based Patient Series |
| title_full_unstemmed | Prognostic Features and Potential for Immune Therapy in Metastatic Mismatch Repair‐Deficient Colorectal Cancer: A Retrospective Analysis of a Large Consecutive Population‐Based Patient Series |
| title_short | Prognostic Features and Potential for Immune Therapy in Metastatic Mismatch Repair‐Deficient Colorectal Cancer: A Retrospective Analysis of a Large Consecutive Population‐Based Patient Series |
| title_sort | prognostic features and potential for immune therapy in metastatic mismatch repair deficient colorectal cancer a retrospective analysis of a large consecutive population based patient series |
| url | https://doi.org/10.1002/cam4.70555 |
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