Immunotherapy for Kidney Cancer

Learn how immunotherapy is transforming the treatment of kidney cancer

What Is Kidney Cancer?

Kidney cancer is the 14th most common cancer worldwide, with an estimated 434,000 new cases diagnosed and approximately 155,700 deaths in 2022, according to the latest GLOBOCAN report. In the U.S., kidney cancer is among the 10 most commonly diagnosed cancers, with an estimated 80,450 new cases and 15,160 deaths expected in 2026. It most often affects adults ages 55–74 and occurs about twice as frequently in men as in women.

Kidney cancer develops in the tissues of the kidneys, the two bean-shaped organs that filter blood and produce urine. Approximately 9 out of 10 kidney cancers are renal cell carcinomas (RCC), which arise from the lining of the tiny tubes inside the kidney. The predominant subtype is clear cell renal cell carcinoma, accounting for about 70-80% of RCC cases. 

Unlike some other cancers, there is currently no routine screening for kidney cancer, and it often develops without obvious symptoms. This makes awareness of risk factors especially important — smoking, obesity, and high blood pressure as well as long-term dialysis and certain hereditary conditions, such as von Hippel-Lindau (VHL) disease, increase risk. 

The five-year survival rate for kidney cancer detected early is 93%. Once the cancer has spread to nearby tissues, five-year survival rates drop to 76% and down to 19% when it has spread to distant parts of the body. Ongoing research is expanding the role of immunotherapy and exploring how immune-based treatments can help more people with kidney cancer.

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What Is Kidney Cancer Screening, and How is Kidney Cancer Detected?

There is currently no routine screening test recommended for kidney cancer in people of average risk. As a result, kidney cancer is often detected incidentally during imaging studies, such as CT scans or ultrasounds, performed for unrelated medical reasons. Kidney cancer may also be detected after symptoms develop, such as blood in the urine, persistent pain in the side, or an unexplained mass.

When kidney cancer is suspected, several tests may be used to confirm the diagnosis:

• Imaging studies: A CT scan, MRI, or ultrasound can help identify tumors in the kidney and determine whether the cancer has spread.
• Biopsy: In some cases, a small tissue sample may be taken to confirm the diagnosis and identify the type of kidney cancer.

Individuals with certain hereditary conditions may be recommended for regular imaging surveillance. VHL disease is a rare genetic disorder marked by the development of tumors and cysts in multiple organs, including the brain, spinal cord, kidneys, pancreas, and eyes. It is caused by mutations in the VHL tumor suppressor gene, which disrupt normal regulation of blood vessel growth and promote tumor formation. Although many of the tumors are benign, some can become cancerous.

Talk to your health care team about whether monitoring may be appropriate based on your individual risk factors.

What Are the Symptoms of Kidney Cancer?

Kidney cancer often does not cause symptoms in its early stages. When symptoms do occur, they may be mild at first and can overlap with those of other conditions.

Possible symptoms of kidney cancer include:

• Blood in the urine
• Persistent pain in the side or lower back
• A lump or mass in the abdomen
• Unexplained weight loss
• Fatigue
• Fever

If you are experiencing ongoing or unusual symptoms, talk to your health care team.

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Can Kidney Cancer Be Prevented?

There is no known way to completely prevent kidney cancer, but certain lifestyle choices may help reduce risk. Avoiding tobacco, maintaining a healthy weight, staying physically active, and managing high blood pressure are all associated with a lower risk of developing kidney cancer.

Some people have a higher risk of developing kidney cancer due to hereditary conditions or family history. For those at increased risk, regular medical care and discussion with a doctor may help support earlier detection and timely evaluation of symptoms.

How Is Kidney Cancer Treated?

Treatment for kidney cancer depends on the stage of the disease, the type and subtype of kidney cancer, and the patient’s overall health. Standard treatment options include surgery (partial or radical nephrectomy, which is the removal of part or all of the kidney), targeted therapy, and immunotherapy. 

For newly diagnosed advanced or metastatic kidney cancer, immunotherapy is now a cornerstone of first-line treatment (the first treatment given for a disease) and has significantly improved survival outcomes over the past decade.

Kidney cancer has a long history with immunotherapy. It was one of the first cancers to be treated with immune-based approaches. In 1992, high-dose interleukin-2 (IL-2) became the first immunotherapy ever approved by the U.S. Food and Drug Administration (FDA) for the treatment of any cancer, marking a pivotal milestone for the field.

Immunotherapies Used to Treat Kidney Cancer

Immunotherapy is a type of cancer treatment that uses your body’s immune system to recognize and attack cancer cells. It works by helping the immune system overcome cancer’s defenses, enabling immune cells to better identify and fight the disease.

Immune checkpoint inhibitors (ICIs) are a type of immunotherapy that blocks immune checkpoints, such as PD-1, PD-L1, or CTLA-4, and are the most widely approved immunotherapy approach for kidney cancer. They are most often used in combination with targeted therapies.

Several FDA-approved immunotherapy regimens are available for kidney cancer. 

First-line treatments (those used as initial therapy before others are tried) include the following ICI-based combinations for advanced RCC:

• Nivolumab (Opdivo®) + ipilimumab (Yervoy®): Approved as first-line treatment for patients with intermediate- or poor-risk advanced RCC. It is a dual ICI combination targeting PD-1 and CTLA-4 pathways.
• Pembrolizumab (Keytruda®) + axitinib (Inlyta®): Approved as first-line treatment for patients with advanced RCC across all risk groups. It combines a PD-1 ICI with a VEGF receptor tyrosine kinase inhibitor (TKI).
• Avelumab (Bavencio®) + axitinib (Inlyta): Approved as first-line treatment for patients with advanced RCC. It combines a PD-L1 ICI with a VEGF receptor TKI.
• Nivolumab (Opdivo) + cabozantinib (Cabometyx®): Approved as first-line treatment for patients with advanced RCC. It combines a PD-1 ICI with a multi-target TKI.
• Pembrolizumab (Keytruda) + lenvatinib (Lenvima®): Approved as first-line treatment for patients with advanced RCC. It combines a PD-1 ICI with a multi-target TKI.

ICI monotherapy (second-line):

• Nivolumab (Opdivo®): Approved in 2015 as a single agent for patients with advanced RCC who have received prior anti-angiogenic therapy. It is a PD-1 ICI and was the first ICI approved for kidney cancer.

Adjuvant immunotherapy (post-surgery):

• Pembrolizumab (Keytruda): Approved in 2021 as adjuvant treatment for patients with RCC at intermediate-high or high risk of recurrence following nephrectomy. It is a PD-1 ICI.

Targeted Therapies Used to Treat Kidney Cancer

Targeted therapies are designed to interfere with specific molecules involved in cancer cell growth and survival. Unlike immunotherapy, which activates the immune system, these treatments directly block the pathways tumors rely on to grow and spread. These include:

• VEGF/VEGFR-targeted therapies: Targeted treatments that block the blood vessel growth pathways that tumors rely on. Treatments in this class include sunitinib (Sutent®), cabozantinib (Cabometyx®), pazopanib (Votrient®), axitinib (Inlyta), lenvatinib (Lenvima®), tivozanib (Fotivda®), and sorafenib (Nexavar®). They are approved for patients with advanced RCC and are used both alone and in combination with immunotherapy.
• mTOR inhibitors: Targeted treatments that block the mTOR signaling pathway involved in cancer cell growth. Treatments in this class include everolimus (Afinitor®) and temsirolimus (Torisel®). They are approved for patients with advanced RCC after prior treatment.
• HIF-2ɑ inhibitors: Targeted treatments that block hypoxia-inducible factor pathways involved in tumor growth. Belzutifan (Welireg®) is approved for patients with VHL disease-associated RCC and for advanced RCC that has progressed after prior immunotherapy and VEGF-TKI treatment.

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Are There Clinical Trials for Patients with Kidney Cancer?

If standard treatments have not worked or are not available, clinical trials may offer access to promising new therapies. Clinical research is progressing across several types of immunotherapy approaches:

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How Is CRI Advancing Kidney Cancer Research?

Kidney cancer has played a pivotal role in the history of cancer immunotherapy — and CRI has been part of that story from the beginning. CRI funds many types of kidney cancer research, from early laboratory discoveries to innovative clinical trials. Our support has helped scientists and clinicians understand how the immune system recognizes kidney tumors, develop new immunotherapy combinations, and identify biomarkers to guide treatment decisions.

In 1978, CRI funded a clinical trial of interferon-alpha (IFN-α) in human patients, work that first demonstrated kidney cancer’s sensitivity to immunotherapy and paved the way for interferon’s FDA approval. CRI also funded research that contributed to the understanding of the PD-1 checkpoint pathway, the science underlying today’s most widely used immunotherapies to treat cancer, including kidney cancer. CRI bestowed its prestigious William B. Coley Award to researchers whose work led to the development of nivolumab and other PD-1/PD-L1 inhibitors.

In 2024, CRI announced a collaboration with the Kidney Cancer Association (KCA) to co-fund kidney cancer immunotherapy research through the CRI Clinic and Laboratory Integration Program (CLIP). This partnership focuses on early detection, reducing treatment side effects, and improving patient quality of life.

Today, CRI continues to fund scientists exploring new frontiers in kidney cancer immunotherapy, including identifying new immune escape mechanisms, understanding the role of the tumor microenvironment, and developing next-generation therapies.

• CRI CLIP Investigator David Braun, MD, PhD, at Yale School of Medicine, is working to develop antigen-directed therapies by mapping the kidney tumor microenvironment to better understand how immune cells recognize and attack kidney cancer.
• CRI CLIP Investigator Allison May, MD, at the University of Virginia, is identifying biomarkers to predict recurrence and immunotherapy response, with the goal of guiding more personalized treatment decisions for kidney cancer patients.
• CRI CLIP Investigator Sidi Chen, PhD, at Yale University received funding to develop novel drug delivery mechanisms targeting kidney tumor cells, aiming to improve how therapies reach and destroy cancer.