The prognostic effect of tumor-associated macrophages in stage I-III colorectal cancer depends on T cell infiltration

Area of Science:

• Immunology
• Oncology
• Pathology

Background:

• Tumor-associated macrophages (TAMs) exhibit diverse roles in cancer, with subsets potentially improving patient prognosis.
• Conflicting data exists regarding the prognostic value of TAMs in colorectal cancer (CRC).
• Investigating TAMs alongside T cells is crucial for understanding CRC progression.

Purpose of the Study:

• To clarify the prognostic significance of TAMs in colorectal cancer.
• To evaluate the interplay between TAMs and tumor-infiltrating T cells (TILs) in CRC.
• To determine if combined immune cell profiling enhances prognostic accuracy in CRC.

Main Methods:

• Multiplex fluorescence immunohistochemistry and digital image analysis of TAM markers (CD68, CD163) and T cell markers (CD3, CD8) in 1720 CRC tissues.
• Quantification of TAM and T cell densities in tumor stroma and epithelium.
• Cox proportional hazards models and multivariable survival analyses incorporating clinicopathological factors, MSI, and BRAF status.

Main Results:

• High TAM density correlated with favorable 5-year relapse-free survival in Stage I-III CRC (HR 0.94, p=0.004).
• Prognostic effect of TAMs was significantly modulated by T cell density (p_interaction=0.0006).
• High TAMs predicted good prognosis with high T cells, but poor prognosis with low T cells, particularly in microsatellite stable tumors.

Conclusions:

• TAMs display phenotypic heterogeneity in colorectal cancer, influencing prognosis differently based on the tumor immune microenvironment.
• Combined immunophenotyping of TAMs and T cells offers improved prediction of patient outcomes in CRC.
• This approach may refine risk stratification and guide therapeutic strategies in colorectal cancer.