Immunoscore encompassing CD3+ and CD8+ T cell densities in distant metastasis is a robust prognostic marker for advanced colorectal cancer

Abstract

Background: The immunoscore (IS), an index based on the density of CD3+ and CD8 + tumor-infiltrating lymphocytes (TILs) in the tumor center (CT) and invasive margin (IM), has gained considerable attention as a prognostic marker. Tumorassociated macrophages (TAMs) have also been reported to have prognostic value. However, its clinical significance has not been fully clarified in patients with advanced CRC who present with distant metastases.Methods: The density of CD3 + , CD4 + , CD8 + , FOXP3 + , CD68 + , and CD163 + immune cells within CRC tissue procured from three sites-the primary CT, IM, and distant metastasis (DM)-was determined using immunohistochemistry and digital image analyzer (n=196). The IS was obtained by quantifying the densities of CD3 + and CD8 + TILs in the CT and IM. IS-metastatic and IS-macrophage-additional IS models designed in this study-were obtained by adding the score of CD3 and CD8 in DM and the score of CD163 in primary tumors (CT and IM), respectively, to the IS.Result: Higher IS, IS-metastatic, and IS-macrophage values were significantly correlated with better prognosis (p=0.020, p≤0.001, and p=0.005, respectively). Multivariate analysis revealed that only IS-metastatic was an independent prognostic marker (p=0.012). No significant correlation was observed between KRAS mutation and three IS models. However, in the subgroup analysis, IS-metastatic showed a prognostic association regardless of the KRAS mutational status.Conclusion: IS is a reproducible method for predicting the survival of patients with advanced CRC. Additionally, an IS including the CD3 + and CD8 + TIL densities at DM could be a strong prognostic marker for advanced CRC.

The prognostic value of immunoscore in patients with colorectal cancer: A systematic review and meta‐analysis

“…After revision, 16 of these 24 papers were excluded for following reasons: eight studies did not provide HRs or CIs, seven studies were reviews, and one study was case report. Therefore, eight studies fulfilled our eligibility criteria for the analysis . Among them, one paper reported the results of two different population respectively, so it was treated as two studies for analysis.…”

“…Therefore, eight studies fulfilled our eligibility criteria for the analysis. 11,[21][22][23][24][25][26][27] Among them, one paper 24 reported the results of two different population respectively, so it was treated as two studies for analysis. Table 1 presented the characteristics of the eight included studies.…”

Assessing Tumor-infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method From the International Immunooncology Biomarkers Working Group: Part 1: Assessing the Host Immune Response, TILs in Invasive Breast Carcinoma and Ductal Carcinoma In Situ, Metastatic Tumor Deposits and Areas for Further Research

“…As discussed in part 2 of this review, TILs in melanoma metastases have been shown to have similar prognostic importance to those in the primary lesion [103–106]. TILs in liver and lung metastases of colorectal carcinoma also show prognostic significance [107–109]. An interesting observation comparing primary breast tumors and later in-breast relapses, based on a very small cohort, is that higher levels of TILs may be associated with true recurrence type relapses while new primary type relapses show lower TIL levels [110].…”

Density and location of CD3+ and CD8+ tumor‐infiltrating lymphocytes correlate with prognosis of oral squamous cell carcinoma

“…In particular, diverse types of tumor‐infiltrating lymphocytes (TILs) produced different effects on tumor growth, recurrence, and metastatic spreading . Accumulating evidence has shown that the presence of TILs is significantly correlated with prognosis of various solid tumors, such as head neck squamous cell carcinoma (HNSCC), gastric cancer, colorectal cancer, breast cancer, and non‐small cell lung cancer . Currently, the most common markers for TILs are CD3 and CD8 which label pan‐T and cytotoxic T cells, respectively.…”