What Can Influence Immunotherapy Responses in Kidney Cancer?

During a presentation at the 2025 Kidney Cancer Research Summit, Dr. Berkay Simsek, a research fellow in pathology at Brigham and Women’s Hospital, discussed how tumor-associated macrophages (TAMs) may influence response to immunotherapy in metastatic clear cell renal cell carcinoma (ccRCC).

TAMs are among the primary immune cells that infiltrate tumors. TAMs are often linked to making cancer harder to treat in cancers like colorectal and pancreatic cancers; however, they may play a different role in Hodgkin lymphoma, where they’ve been associated with better treatment response. Simsek noted that their role in predicting clinical outcomes remains uncertain, especially in ccRCC. 

Dr. Simsek’s research looked at whether high levels of a specific kind of TAM (CD163-positive) are linked to better results with first-line PD-1 immunotherapy using Opdivo (nivolumab). His findings suggest that these immune cells might be reprogrammed by treatment to switch from helping the tumor grow to helping the immune system fight it.

He also studied how TAMs interact with other immune cells in specific areas within tumors. Understanding these interactions, particularly in pretreatment samples, could help identify which patients are more likely to benefit from immunotherapy.

“The target of immunotherapy is actually immune cells in the tumor microenvironment, not the tumor itself,” Simsek said. By studying which immune cells express key markers and how they relate to clinical outcomes like progression-free survival or response rate, researchers may be able to refine how and when immunotherapy is used.

Transcript

How might understanding immune cells in a tumor help predict which patients or responding well to immunotherapy?

The target of immunotherapy is actually immune cells in the tumor microenvironment, not the tumor itself. Different immunotherapies have different targets on these immune cells, and it's important to understand which immune cells express those markers. Also, understanding the composition of the tumor microenvironment — especially in pretreatment samples — and analyzing that in relation to outcomes like progression-free survival or objective response rate is important.

Reference

1. “Simsek S. CD163+ tumor-associated macrophages and clinical outcomes to first-line nivolumab therapy in patients with metastatic clear cell renal cell carcinoma: insights from the HCRN GU16-260 trial.” Presented at: 2025 Kidney Cancer Research Summit, July 17 to 18, 2025.

Transcript has been edited for clarity and conciseness.

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