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Prognostic and predictive value of tumor infiltrating lymphocytes in combination with systemic inflammatory markers in colon cancer - 11/08/23

Doi : 10.1016/j.clinre.2023.102171 
Safa Can Efil a, Gunes Guner b, Deniz Can Guven a, Burcu Celikten a, Elvin Celebiyev a, Hakan Taban a, Aytekin Akyol b, Aynur Isik c, Sadettin Kilickap d, Suayib Yalcin a, Omer Dizdar d,
a Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey 
b Department of Pathology, Hacettepe University Faculty of Medicine, Ankara, Turkey 
c Hacettepe University Transgenic Animal Technologies Research and Application Center, Ankara, Turkey 
d Department of Preventive Oncology, Hacettepe University Cancer Institute, Ankara, Turkey 

Corresponding author.

Highlights

Systemic inflammatory indices such as neutrophil/lymphocyte ratio or prognostic nutrition index are highly prognostic in colon cancer. CD8(+) tumor infiltrating lymphocytes (TILs) are also associated with favorable prognosis in colon cancer while the lack of lymphocytic infiltration usually shows poor prognosis.
In this study, among patients with resected stage II-III colon cancer, a novel “combined inflammatory score” (CIS) was defined, with classifying patients with high systemic inflammation (in terms of pan-immune inflammation value -PIV) and low CD8(+) tumor infiltrating lymphocytes as high CIS.
High CIS (PIVhigh / CD8low) was independently associated with shorter DFS. Among patients with stage II disease, those with high CIS (PIVhigh / CD8low) derived significant benefit from adjuvant chemotherapy while the patients with low CIS did not.

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Abstract

Objective. Systemic inflammatory indices and CD8(+) tumor infiltrating lymphocytes (TILs) in the tumor microenvironment are highly prognostic in colon cancer (CC) but combined assessment is less well studied. The purpose of this study was to investigate the prognostic and predictive value of CD8(+) TILs in combination with systemic inflammatory indices in patients with resected stage II-III colon cancer.

Patients and methods. Patients with stage II-III CC (n = 304) diagnosed between 2008 and 2016 were included. Pan-immune inflammation value (PIV) was used as a comprehensive inflammatory index and was calculated as: [neutrophil count × platelet count × monocyte count]/lymphocyte count. The mean density of CD8+ TILs in the periphery and center of the tumor was assessed and dichotomized at the 75th percentile. Combined inflammation score (CIS) was classified as “high” in patients with high PIV (>median) plus low mean CD8(+) TILs density, and CIS “low” in the remaining patients.

Results. 5-year DFS was 71% (78% in stage II, 63.4% in stage III). PIV was higher in right colon tumors, T4 tumors and in patients with obstruction / perforation. CD8(+) TIL density was lower in node positive tumors. High PIV and low CD8(+) TILs were associated with shorter disease-free survival (DFS). In multivariate analysis; age > 65 years, stage III disease and high CIS (PIVhigh / CD8low) were associated with shorter DFS. Among patients with stage II disease, patients with high CIS (PIVhigh / CD8low) derived significant benefit from adjuvant chemotherapy while those with low CIS derived no benefit.

Conclusion. Combined inflammation score may represent a new prognostic factor for localized colon cancer and predictor of chemotherapy response in patients with stage II disease.

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Keywords : Colon cancer, Systemic inflammation, CD8 infiltration, prognosis


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Vol 47 - N° 7

Article 102171- août 2023 Retour au numéro
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