The following is a summary of “Immune Landscape of renal cell carcinoma with metastasis to the pancreas,” published in the July 2024 issue of Urology by Kippenberger et al.

Clear cell Renal Cell Carcinoma (ccRCC) is notorious for its dismal prognosis upon metastasis, yet the site of metastasis can significantly influence patient outcomes. Notably, metastases to the pancreas are associated with a more favorable prognosis compared to metastases in other organs, though the underlying biological mechanisms driving this phenomenon remain poorly understood. This study aimed to delineate the immune landscape of pancreatic metastases and corresponding primary tumors of ccRCC to identify potential immunological correlates influencing disease biology.

Researchers conducted a comprehensive analysis using 1,700 microscopic images derived from ccRCC primary tumors and their pancreatic metastases in 11 patients, alongside ccRCC tumors from 10 patients without pancreatic involvement. Immunohistochemical staining for CD45, CD8, CD163, and FOXP3 was performed, with a semiquantitative assessment of immune cell densities in both intratumoral and extratumoral regions. Selected tumors underwent multispectral imaging for further characterization.

The findings revealed that pancreatic metastases exhibited the lowest intratumoral infiltration of CD8⁺ cytotoxic T lymphocytes compared to primary tumors and ccRCCs without pancreatic involvement. Specifically, the median density of CD8⁺ lymphocytes was significantly lower in pancreatic metastases (8.3 cells per field of view [FOV] = 1.23 mm²) compared to primary tumors (15.6 cells per FOV, P = 0.0002) and ccRCCs without pancreatic metastases (27.2 cells per FOV, P = 0.0012). Similarly, there was a marked reduction in intratumoral FOXP3⁺ immunosuppressive lymphocytes in pancreatic metastases (2.6 cells per FOV, P = 0.009) and corresponding primary tumors (2 cells per FOV, P = 0.028) compared to ccRCCs without pancreatic involvement (5.6 cells per FOV).

This proof-of-concept study highlights distinct immunological features in ccRCC pancreatic metastases, characterized by diminished intratumoral densities of CD8⁺ and FOXP3⁺ lymphocytes. These findings suggest that the attenuated immune cell infiltration observed in pancreatic metastases may contribute to less aggressive disease characteristics, potentially contributing to the more favorable prognosis associated with these metastases. Further elucidation of these immunological dynamics could offer insights into novel therapeutic strategies tailored to specific metastatic patterns in ccRCC.

Source: sciencedirect.com/science/article/pii/S1078143924005027