Tumor-infiltrating macrophages and dendritic cells in human colorectal cancer: relation to local regulatory T cells, systemic T-cell response against tumor-associated antigens and survival - PubMed (original) (raw)
Tumor-infiltrating macrophages and dendritic cells in human colorectal cancer: relation to local regulatory T cells, systemic T-cell response against tumor-associated antigens and survival
Dirk Nagorsen et al. J Transl Med. 2007.
Abstract
Introduction: Although systemic T-cell responses against tumor antigens and tumor infiltration by T cells have been investigated in colorectal cancer (CRC), the initiation of spontaneous immune responses in situ is not well understood. Macrophages and dendritic cells (DC) play an important role as a link between innate and adaptive immune response. The aim of the present study was to analyze macrophage and DC infiltration in CRC and to investigate whether there is a correlation to systemic T-cell response, regulatory T cell (Treg) infiltration, and survival.
Methods: Immunohistological staining was performed with nine markers for macrophages and DC (CD68, CD163, S100, CD11c, CD208, CD209, CD123, CD1a, Langerin) in 40 colorectal cancer samples from patients, in whom the state of systemic T-cell responses against tumor-associated antigens (TAA) and Treg infiltration had previously been determined.
Results: All specimens contained cells positive for CD68, CD163, S100 and CD1a in epithelial tumor tissue and tumor stroma. Only a very few (less than median 3/HPF) CD123+, CD1a+, CD11c+, CD 208+, CD209+, or Langerin+ cells were detected in the specimens. Overall, we found a trend towards increased infiltration by S100-positive DC and a significantly increased number of stromal S100-positive DC in patients without T-cell response. There was an increase of stromal S100 DC and CD163 macrophages in limited disease (S100: 11.1/HPF vs. 7.3/HPF, p = 0.046; CD163: 11.0/HPF vs. 8.1/HPF, p = 0.06). We found a significant, positive correlation between S100-positive DC and FOXP3-positive Tregs. Survival in patients with high DC infiltration was significantly better than that in those with low DC infiltration (p < 0.05). Furthermore, we found a trend towards better survival for increased infiltration with CD163-positive macrophages (p = 0.07).
Conclusion: The present in situ study adds new data to the discussion on the interaction between the innate and adoptive immune system. Our data strongly support the hypothesis that tumor-infiltrating DC are a key factor at the interface between innate and adaptive immune response in malignant disease. Tumor infiltrating S100-positive DC show an inverse relationship with the systemic antigen-specific T-cell response, a positive correlation with regulatory T cells, and a positive association with survival in CRC. These data put tumor-infiltrating DC at the center of the relevant immune response in CRC.
Figures
Figure 1
Immunohistochemical staining of macrophage and dendritic cell infiltration in colorectal cancer. (A) CD68 and (B) CD163 expression of the macrophages (inset: double labeling CD163 (red)/S100 (brown) distinguishes CD163+ macrophages from S100+ DC). Dendritic cell populations with expression of (C) S100, (D) CD11c, (E) CD208, (F) CD209, (G) CD123 and (H) CD1a (inset: Langerin/CD207). (magnification ×200, inset ×400).
Figure 2
Kaplan Meier survival analyses of patients with high (solid) and low (dashed) cell infiltration in the tumor. A) Patients with high S100 infiltration have a significantly better survival (p = 0.03). B) Patients with high total CD163 tend to have a better survival (p = 0.07). C) Patients with high stromal CD163 infiltration have a significantly better survival (p = 0.01).
Similar articles
- Dendritic cell and macrophage infiltration in microsatellite-unstable and microsatellite-stable colorectal cancer.
Bauer K, Michel S, Reuschenbach M, Nelius N, von Knebel Doeberitz M, Kloor M. Bauer K, et al. Fam Cancer. 2011 Sep;10(3):557-65. doi: 10.1007/s10689-011-9449-7. Fam Cancer. 2011. PMID: 21598004 - Prognostic value of tumor-infiltrating dendritic cells in colorectal cancer: role of maturation status and intratumoral localization.
Sandel MH, Dadabayev AR, Menon AG, Morreau H, Melief CJ, Offringa R, van der Burg SH, Janssen-van Rhijn CM, Ensink NG, Tollenaar RA, van de Velde CJ, Kuppen PJ. Sandel MH, et al. Clin Cancer Res. 2005 Apr 1;11(7):2576-82. doi: 10.1158/1078-0432.CCR-04-1448. Clin Cancer Res. 2005. PMID: 15814636 - High infiltration of CD209+ dendritic cells and CD163+ macrophages in the peritumor area of prostate cancer is predictive of late adverse outcomes.
Molina OE, LaRue H, Simonyan D, Hovington H, Têtu B, Fradet V, Lacombe L, Toren P, Bergeron A, Fradet Y. Molina OE, et al. Front Immunol. 2023 Jun 26;14:1205266. doi: 10.3389/fimmu.2023.1205266. eCollection 2023. Front Immunol. 2023. PMID: 37435060 Free PMC article. - Tumor Infiltrating Regulatory T Cells in Sporadic and Colitis-Associated Colorectal Cancer: The Red Little Riding Hood and the Wolf.
Fantini MC, Favale A, Onali S, Facciotti F. Fantini MC, et al. Int J Mol Sci. 2020 Sep 14;21(18):6744. doi: 10.3390/ijms21186744. Int J Mol Sci. 2020. PMID: 32937953 Free PMC article. Review. - Systemic Interleukins' Profile in Early and Advanced Colorectal Cancer.
Czajka-Francuz P, Cisoń-Jurek S, Czajka A, Kozaczka M, Wojnar J, Chudek J, Francuz T. Czajka-Francuz P, et al. Int J Mol Sci. 2021 Dec 23;23(1):124. doi: 10.3390/ijms23010124. Int J Mol Sci. 2021. PMID: 35008550 Free PMC article. Review.
Cited by
- Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives.
Shi X, Wang X, Yao W, Shi D, Shao X, Lu Z, Chai Y, Song J, Tang W, Wang X. Shi X, et al. Signal Transduct Target Ther. 2024 Aug 2;9(1):192. doi: 10.1038/s41392-024-01885-2. Signal Transduct Target Ther. 2024. PMID: 39090094 Free PMC article. Review. - Molecular subtypes of clear cell renal carcinoma based on PCD-related long non-coding RNAs expression: insights into the underlying mechanisms and therapeutic strategies.
Wang H, Liu Y, Tang A, Zhang X. Wang H, et al. Eur J Med Res. 2024 May 21;29(1):292. doi: 10.1186/s40001-024-01883-8. Eur J Med Res. 2024. PMID: 38773560 Free PMC article. - Molecular insights into clinical trials for immune checkpoint inhibitors in colorectal cancer: Unravelling challenges and future directions.
Sharma S, Singh N, Turk AA, Wan I, Guttikonda A, Dong JL, Zhang X, Opyrchal M. Sharma S, et al. World J Gastroenterol. 2024 Apr 7;30(13):1815-1835. doi: 10.3748/wjg.v30.i13.1815. World J Gastroenterol. 2024. PMID: 38659481 Free PMC article. Review. - Transient TCR-based T cell therapy in a patient with advanced treatment-resistant MSI-high colorectal cancer.
Maggadottir SM, Dueland S, Mensali N, Hamre H, Andresen PA, Myhre MR, Juul HV, Bigalke I, Lundby M, Hønnåshagen TK, Sæbøe-Larssen S, Josefsen D, Hagtvedt T, Wälchli S, Kvalheim G, Inderberg EM. Maggadottir SM, et al. Mol Ther. 2024 Jun 5;32(6):2021-2029. doi: 10.1016/j.ymthe.2024.04.009. Epub 2024 Apr 6. Mol Ther. 2024. PMID: 38582964 - Decreased interleukin-17RA expression is associated with good prognosis in patients with colorectal cancer and inhibits tumor growth and vascularity in mice.
Jiang JK, Lin CH, Chang TA, Lo LC, Lin CP, Lu RH, Yang CY. Jiang JK, et al. Cancer Med. 2024 Mar;13(5):e7059. doi: 10.1002/cam4.7059. Cancer Med. 2024. PMID: 38491831 Free PMC article.
References
- Naito Y, Saito K, Shiiba K, Ohuchi A, Saigenji K, Nagura H, Ohtani H. CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res. 1998;58:3491–3494. - PubMed
- Funada Y, Noguchi T, Kikuchi R, Takeno S, Uchida Y, Gabbert HE. Prognostic significance of CD8+ T cell and macrophage peritumoral infiltration in colorectal cancer. Oncol Rep. 2003;10:309–13. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials