Linking Transcriptomic and Imaging Data Defines Features of a Favorable Tumor Immune Microenvironment and Identifies...

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• Resected stage II-III melanoma patients face a significant risk of disease-specific death (DSS).
• Understanding the tumor immune microenvironment (TIME) is crucial for patient stratification and overcoming therapy resistance.
• Previous work identified the melanoma immune profile (MIP) and CD8+ cytotoxic T lymphocyte (CTL) to CD68+ macrophage ratio as predictors of DSS.

Purpose of the Study:

• To compare primary and metastatic melanoma tumors to identify differences in the TIME.
• To investigate the relationship between immune cell infiltration, tumor cell characteristics, and patient outcomes.
• To develop a combined biomarker strategy for improved risk stratification in melanoma patients.

Main Methods:

• Comparative analysis of primary versus metastatic melanoma tumors.
• Assessment of tumor cell nuclear size and immune cell infiltration (CTLs, macrophages).
• Multiplex and transcriptomic analyses to correlate immune cell phenotypes with gene signatures.

Main Results:

• Metastatic tumors exhibited larger tumor cell nuclei compared to primary tumors.
• The CTL/macrophage ratio differed significantly between primary tumors and metastases.
• Patients without distant metastatic recurrence (DMR) showed increased clustering of tumor cells with CTLs and HLA-DR+ macrophages.
• HLA-DR- macrophages displayed an M2 phenotype, co-expressing CD163 and CSF1R.
• Combined MIP signature and CTL/macrophage ratio stratified patients into three distinct risk groups predictive of DSS.

Conclusions:

• Combined transcriptomic and multiplex data reveal correlations between CD8+ T cell and M1 macrophage densities and their respective cell phenotype signatures.
• The combination of MIP signature and CTL/macrophage ratio offers a powerful tool for stratifying melanoma patients.
• This multi-modal approach enhances understanding of the TIME and aids in developing improved adjuvant therapy strategies for melanoma.