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
Wirta, E., Elomaa, H., Mecklin, J., Seppälä, T. T., Hyöty, M., Böhm, J., Ahtiainen, M., & Väyrynen, J. P. (2025). 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, 14(1), Article e70555. https://doi.org/10.1002/cam4.70555
Julkaistu sarjassa
Cancer MedicineTekijät
Päivämäärä
2025Tekijänoikeudet
© 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.
2025:11
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.
...
Julkaisija
John Wiley & SonsISSN Hae Julkaisufoorumista
2045-7634Asiasanat
Julkaisu tutkimustietojärjestelmässä
https://converis.jyu.fi/converis/portal/detail/Publication/245024742
Metadata
Näytä kaikki kuvailutiedotKokoelmat
Lisätietoja rahoituksesta
EW was supported by the Finnish Medical Foundation, the Mary and Georg C. Ehrnrooth Foundation, the Cancer Foundation of Finland, andthe Ida Montin Foundation. TTS was supported by the Cancer Foundation of Finland, the Jane and Aatos Erkko Foundation, the Emil Aaltonen Foundation,the Sigrid Jusélius Foundation, the Relander Foundation, and the iCAN Flagship of the Academy of Finland; JPM was supported by the Cancer Foundationof Finland, the Jane and Aatos Erkko Foundation, and Finnish State Research Funding; and JPV was supported by the Cancer Foundation of Finland andthe Sigrid Jusélius Foundation. ...Lisenssi
Samankaltainen aineisto
Näytetään aineistoja, joilla on samankaltainen nimeke tai asiasanat.
-
Impact of Primary Tumor Location on Demographics, Resectability, Outcomes, and Quality of Life in Finnish Metastatic Colorectal Cancer Patients (Subgroup Analysis of the RAXO Study)
Aho, Sonja; Osterlund, Emerik; Ristimäki, Ari; Nieminen, Lasse; Sundström, Jari; Mäkinen, Markus J.; Kuopio, Teijo; Kytölä, Soili; Ålgars, Annika; Ristamäki, Raija; Heervä, Eetu; Kallio, Raija; Halonen, Päivi; Soveri, Leena-Maija; Nordin, Arno; Uutela, Aki; Salminen, Tapio; Stedt, Hanna; Lamminmäki, Annamarja; Muhonen, Timo; Kononen, Juha; Glimelius, Bengt; Isoniemi, Helena; Lehto, Juho T.; Lehtomäki, Kaisa; Osterlund, Pia (MDPI AG, 2024)The primary tumor location (PTL) is associated with the phenotype, metastatic sites, mutations, and outcomes of metastatic colorectal cancer (mCRC) patients, but this has mostly been studied according to sidedness (right ... -
Mitotic abnormalities precede microsatellite instability in lynch syndrome-associated colorectal tumourigenesis
Pussila, Marjaana; Laiho, Aleksi; Törönen, Petri; Björkbacka, Pauliina; Nykänen, Sonja; Pylvänäinen, Kirsi; Holm, Liisa; Mecklin, Jukka-Pekka; Renkonen-Sinisalo, Laura; Lehtonen, Taru; Lepistö, Anna; Linden, Jere; Mäki-Nevala, Satu; Peltomäki, Päivi; Nyström, Minna (Elsevier, 2024)Background Lynch syndrome (LS) is one of the most common hereditary cancer syndromes worldwide. Dominantly inherited mutation in one of four DNA mismatch repair genes combined with somatic events leads to mismatch repair ... -
Immunological and prognostic significance of tumour necrosis in colorectal cancer
Kastinen, Meeri; Sirniö, Päivi; Elomaa, Hanna; Ahtiainen, Maarit; Väyrynen, Sara A.; Herzig, Karl-Heinz; Meriläinen, Sanna; Aro, Raila; Häivälä, Reetta; Rautio, Tero; Saarnio, Juha; Wirta, Erkki-Ville; Helminen, Olli; Seppälä, Toni T.; Kuopio, Teijo; Böhm, Jan; Tuomisto, Anne; Mecklin, Jukka-Pekka; Mäkinen, Markus J.; Väyrynen, Juha P. (Nature Publishing Group, 2023)Background Colorectal cancer (CRC) causes the second most cancer deaths worldwide, but the disease course varies according to tumour characteristics and immunological factors. Our objective was to examine the associations ... -
Prognostic significance of spatial and density analysis of T lymphocytes in colorectal cancer
Elomaa, Hanna; Ahtiainen, Maarit; Väyrynen, Sara A.; Ogino, Shuji; Nowak, Jonathan A.; Friman, Marjukka; Helminen, Olli; Wirta, Erkki-Ville; Seppälä, Toni T.; Böhm, Jan; Mäkinen, Markus J.; Mecklin, Jukka-Pekka; Kuopio, Teijo; Väyrynen, Juha P. (Nature Publishing Group, 2022)BACKGROUND: Although high T cell density is a strong favourable prognostic factor in colorectal cancer, the significance of the spatial distribution of T cells is incompletely understood. We aimed to evaluate the prognostic ... -
Incidence and management of patients with colorectal cancer and synchronous and metachronous colorectal metastases : a population-based study
Väyrynen, V.; Wirta, E; Seppälä, T.; Sihvo, E.; Mecklin, J-P.; Vasala, K.; Kellokumpu, I. (John Wiley & Sons, 2020)Background This population-based study aimed to examine the incidence, patterns and results of multimodal management of metastatic colorectal cancer. Methods A retrospective population-based study was conducted on patients ...
Ellei toisin mainittu, julkisesti saatavilla olevia JYX-metatietoja (poislukien tiivistelmät) saa vapaasti uudelleenkäyttää CC0-lisenssillä.