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. 2024 Jan 17;27(3):104.
doi: 10.3892/ol.2024.14237. eCollection 2024 Mar.

Prognostic value of a modified‑immune scoring system in patients with pathological T4 colorectal cancer

Gendensuren Dorjkhorloo  1 , Bilguun Erkhem-Ochir  2 , Takuya Shiraishi  1 , Makoto Sohda  1 , Haruka Okami  1 , Arisa Yamaguchi  1 , Ikuma Shioi  1 , Chika Komine  1 , Nobuhiro Nakazawa  1 , Naoya Ozawa  1 , Yuta Shibasaki  1 , Takuhisa Okada  1 , Katsuya Osone  1 , Akihiko Sano  1 , Makoto Sakai  1 , Hiroomi Ogawa  1 , Takehiko Yokobori  2 , Ken Shirabe  1 , Hiroshi Saeki  1
Affiliations

Prognostic value of a modified‑immune scoring system in patients with pathological T4 colorectal cancer

Gendensuren Dorjkhorloo et al. Oncol Lett. .

Abstract

Tumor-infiltrating immune cells, such as lymphocytes and macrophages, have been associated with tumor aggressiveness, prognosis and treatment response in colorectal cancer (CRC). An immune scoring system, Immunoscore (IS), based on tumor-infiltrating T cells in stage I-III CRC, was used to predict prognosis. An alternative immune scoring signature of immune activation (SIA) reflects the balance between anti- and pro-tumoral immune components. The present study aimed to evaluate the prognostic value of modified IS (mIS) and modified SIA (mSIA) in locally advanced pathological T4 (pT4) CRC, including stage IV CRC. Immunohistochemical staining for immune cell markers, such as CD3 (pan-T cell marker), CD8 (anti-tumoral cytotoxic T cell marker) and CD163 (tumor-supportive macrophage marker), in specimens from patients with radically resected pT4 CRC at stages II-IV was performed. mIS levels in the T4 CRC cohort were not associated with prognosis. However, low mSIA levels were associated with low survival. Furthermore, low mSIA was an independent predictor of recurrence in patients with radically resected pT4 CRC. In patients with CRC who did not receive postoperative adjuvant chemotherapy, low mSIA was a major poor prognostic factor; however, this was not observed in patients receiving adjuvant chemotherapy. Evaluation of the tumor-infiltrating immune cell population could serve as a valuable marker of recurrence and poor prognosis in patients with locally advanced CRC. mSIA assessment after radical CRC resection may be promising for identifying high-risk patients with pT4 CRC who require aggressive adjuvant chemotherapy.

Keywords: Immunoscore; colon cancer; immune cell infiltration; locally advanced colon cancer; prognostic marker; signature of immune activation; tumor immunity.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1.
Figure 1.
Immune marker staining and illustration of image acquisition and analysis. (A) Representative images of high and low immune cell infiltration of CD8+, CD3+ and CD163+ cells at the central tumor and invasive margin. All images were obtained at a magnification of ×200; scale bar, 100 µm. (B) A methodological illustration of image acquisition of CD8+, CD3+ and CD163+ immune cells. The panoramic image was acquired by stitching multiple images captured at ×4 magnification, images showing the hybrid cell counting process were obtained at a magnification of ×200; scale bar, 100 µm.
Figure 2.
Figure 2.
Kaplan-Meier survival curves stratified according to high and low mIS. The top panel shows the overall (left), cancer-specific (middle) and disease-free (right) survival of all patients with pT4 CRC (n=78), according to mIS. The middle panel shows the overall (left), cancer-specific (middle) and disease-free (right) survival of patients with pT4 CRC with postoperative adjuvant chemotherapy (n=50), according to mIS. Patients who underwent adjuvant treatment exhibited indistinguishable overall and cancer-specific survival rates. Within this specific subgroup, all deceased patients succumbed to causes directly linked to cancer. The bottom panel shows the overall (left), cancer-specific (middle) and disease-free (right) survival of patients with pT4 CRC without postoperative adjuvant chemotherapy (n=28), according to mIS. mIS, modified Immunoscore; CRC, colorectal cancer.
Figure 3.
Figure 3.
Kaplan-Meier survival curves stratified according to high and low mSIA. The top panel shows the overall (left), cancer-specific (middle) and disease-free (right) survival of all patients with pT4 CRC (n=78), according to mSIA. The middle panel shows the overall (left), cancer-specific (middle) and disease-free (right) survival of patients with pT4 CRC with postoperative adjuvant chemotherapy (n=50), according to mSIA. Patients who underwent adjuvant treatment exhibited indistinguishable overall and cancer-specific survival rates. Within this specific subgroup, all deceased patients succumbed to causes directly linked to cancer. The bottom panel shows the overall (left), cancer-specific (middle) and disease-free (right) survival of patients with pT4 CRC without postoperative adjuvant chemotherapy (n=28), according to mSIA. mSIA, modified signature of immune activation; CRC, colorectal cancer.
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References

    1. Laghi L, Negri F, Gaiani F, Cavalleri T, Grizzi F, De'Angelis GL, Malesci A. Prognostic and predictive cross-roads of microsatellite instability and immune response to colon cancer. Int J Mol Sci. 2020;21:9680. doi: 10.3390/ijms21249680. - DOI - PMC - PubMed
    1. Brummel K, Eerkens AL, de Bruyn M, Nijman HW. Tumour-infiltrating lymphocytes: From prognosis to treatment selection. Br J Cancer. 2023;128:451–458. doi: 10.1038/s41416-022-02119-4. - DOI - PMC - PubMed
    1. Zhang Q, Sioud M. Tumor-associated macrophage subsets: Shaping polarization and targeting. Int J Mol Sci. 2023;24:7493. doi: 10.3390/ijms24087493. - DOI - PMC - PubMed
    1. Daitoku N, Miyamoto Y, Hiyoshi Y, Tokunaga R, Sakamoto Y, Sawayama H, Ishimoto T, Baba Y, Yoshida N, Baba H. Preoperative skeletal muscle status is associated with tumor-infiltrating lymphocytes and prognosis in patients with colorectal cancer. Ann Gastroenterol Surg. 2022;6:658–666. doi: 10.1002/ags3.12570. - DOI - PMC - PubMed
    1. Melssen MM, Sheybani ND, Leick KM, Slingluff CL., Jr Barriers to immune cell infiltration in tumors. J Immunother Cancer. 2023;11:e006401. doi: 10.1136/jitc-2022-006401. - DOI - PMC - PubMed

Grants and funding

The present study was supported by the Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS; grant nos. 23K14610, 22H02912, 22K08766 and 21K08749).