Introduction:

Tumor-associated macrophages (TAMs) have been associated with tumor progression and metastasis in breast, ovarian and gastric cancers. Based on response to microenvironmental stimuli, TAMs may differentiate into two different types of macrophages: tumor resisting type 1 (M1) and tumor promoting type 2 (M2) macrophages. Using the pan-macrophages marker CD68 and M2 markers CD163 and CD206, we aimed to evaluate the clinical significance of TAM location mapping within the tumor in patients with metastatic renal cell carcinoma (mRCC) treated with immunotherapy.

Methods:

A total of 26 patients treated with immunotherapy for mRCC were included in this pilot study. Patients received either IL-2 (n =20) or checkpoint inhibitors (n=6) as first immune agent. Using quantitative multiplex immunofluorescence (Opal™; PerkinElmer), expression levels of CD68, CD163 and CD206 markers within the tumor nest, at the tumor-stroma interface, and within the surrounding stroma were evaluated in formalin-fixed paraffin-embedded primary tumor samples. Expression densities of CD68⁺, CD68⁺/CD163⁺and CD68⁺/206⁺TAMs were calculated and patients were grouped into low and high expression subgroups stratified by median expression level of each marker. Survival from the date of first immunotherapy was compared between patients with low and high biomarker expressions using a Log-rank test. 

Results:

Our findings (Table 1) demonstrate that high expression of pan-macrophage marker, CD68 within the mRCC microenvironment and high expression of M2 marker of CD68/CD163 in surrounding stroma was associated with poor overall survival of the patients. 

Conclusion:

Certain TAM expression markers correlate with survival of patients with mRCC. High co-expression of TAMs markers within the tumor microenvironment and their location associates with poor survival. Whether or not TAM markers can aid in the treatment decision making process in mRCC remains to be further investigated.

Funding: N/A