Immunotherapy for Kidney Cancer

The goal of immunotherapy (sometimes called biologic therapy) is to boost the body’s immune system to help fight off or destroy cancer cells.


Cytokines are man-made versions of natural proteins that activate the immune system. The cytokines used most often to treat kidney cancer are interleukin-2 (IL-2) and interferon-alpha. Both cytokines can cause kidney cancers to shrink in a small percentage of patients.

Interleukin-2 (IL-2)

In the past, IL-2 was commonly used as first-line therapy for advanced kidney cancer, and it may still be helpful for some people. But it can cause serious side effects, so many doctors only use it for people who are healthy enough to withstand the side effects, or for cancers that aren’t responding to targeted drugs.

Although only a small percentage of patients respond to IL-2, it is the only therapy that appears to result in long-lasting responses. Doctors are now looking to see if certain patient and cancer characteristics can help predict if IL-2 will be helpful.

Giving high doses of IL-2 seems to offer the best chance of shrinking the cancer, but this can cause serious side effects, so it is not used in people who are in poor overall health to begin with. Special care is needed to recognize and treat these side effects. Because of this, high-dose IL-2 is only given in the hospital at certain centers that are experienced with giving this type of treatment. IL-2 is given through a vein (IV).

The possible side effects of high-dose IL-2 include:

  • Extreme fatigue
  • Low blood pressure
  • Fluid buildup in the lungs
  • Trouble breathing
  • Kidney damage
  • Heart attacks
  • Intestinal bleeding
  • Diarrhea or abdominal pain
  • High fever and chills
  • Rapid heart beat
  • Mental changes

These side effects are often severe and, rarely, can be fatal. Only doctors experienced in the use of these cytokines should give this treatment.


Interferon has less serious side effects than IL-2, but it does not seem to be as effective when used by itself. It is more often used in combination with the targeted drug bevacizumab (Avastin). Interferon is given as a subcutaneous injection (under the skin) usually three times a week.

Common side effects of interferon include flu-like symptoms (fever, chills, muscle aches), fatigue, and nausea.

Immune checkpoint inhibitors

An important part of the immune system is its ability to keep itself from attacking normal cells in the body. To do this, it uses “checkpoints,” which are molecules on immune cells that need to be turned on (or off) to start an immune response. Cancer cells sometimes use these checkpoints to avoid being attacked by the immune system. But newer drugs that target these checkpoints hold a lot of promise as cancer treatments.

PD-1 inhibitors

Nivolumab (Opdivo) is a drug that targets PD-1, a protein on immune system cells called T cells that normally helps keep these cells from attacking other cells in the body. By blocking PD-1, this drug boosts the immune response against cancer cells. This can shrink some tumors or slow their growth.

This drug can be used for people whose kidney cancer starts growing again after other drug treatments.

For patients with intermediate or poor risk advanced kidney cancer who have not received any treatment, nivolumab can be given with ipilimumab (a CTLA-4 inhibitor) for 4 doses followed by nivolumab alone. This drug combination has been shown to shrink the tumor significantly as well as help people live longer.

Nivolumab is given as an intravenous (IV) infusion, typically every 2 weeks.

Possible side effects

Side effects of immune checkpoint inhibitors can include fatigue, cough, nausea, itching, skin rash, loss of appetite, constipation, joint pain, and diarrhea.

Other, more serious side effects occur less often. These drugs work by basically removing the brakes on the body’s immune system. Sometimes the immune system starts attacking other parts of the body, which can cause serious or even life-threatening problems in the lungs, intestines, liver, hormone-making glands (like the thyroid), kidneys, or other organs.

It’s very important to report any new side effects to your health care team promptly. If serious side effects do occur, treatment may need to be stopped and you may get high doses of steroids to suppress your immune system and treat the side effects.

CTLA-4 inhibitors

Ipilimumab (Yervoy) is another drug that boosts the immune response, but it has a different target. It blocks CTLA-4, another protein on T cells that normally helps keep them in check.

For patients with intermediate or poor risk advanced kidney cancer who have not received any treatment, ipilimumab can be given with nivolumab (an immune checkpoint inihibitor) for 4 doses followed by nivolumab alone. This drug combination has been shown to shrink the tumor significantly as well as help people live longer.

Ipilimumab is given as an intravenous (IV) infusion, usually once every 3 weeks for 4 treatments.

Possible side effects

The most common side effects from Ipilimumab include fatigue, diarrhea, skin rash, and itching.

Like the PD-1 inhibitors, this drug can cause the immune system to attack other parts of the body, which can lead to serious problems in the intestines, liver, hormone-making glands, nerves, skin, eyes, or other organs. In some people these side effects can be life threatening.

It’s very important to report any new side effects during or after treatment to your health care team promptly. If serious side effects do occur, you may need to stop treatment and take high doses of corticosteroids to suppress your immune system.

More information about immunotherapy

To learn more about how targeted drugs are used to treat cancer, see Cancer Immunotherapy.

To learn about some of the side effects listed here and how to manage them, see Managing Cancer-related Side Effects.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

American Cancer Society. Cancer Facts & Figures 2017. Atlanta, Ga: American Cancer Society; 2017.

Atkins MB. UpToDate. Overview of the treatment of renal cell carcinoma; This topic last updated: Jun 13, 2017. Accessed at on June 16, 2017.

Belldegrun AS, Klatte T, Shuch B, et al. Cancer-specific survival outcomes among patients treated during the cytokine era of kidney cancer (1989-2005): A benchmark for emerging targeted cancer therapies. Cancer. 2008;113:2457-2463.

Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366:2455-2465.

Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007;356:2271-2281.

Lane BR, Canter DJ, Rini BI, Uzzo RG. Ch 63 - Cancer of the kidney. In: DeVita VT, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2015.

McDermott DF, Regan MM, Clark JI, et al. Randomized phase III trial of high dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma. J Clin Oncol. 2005;23:133-141.

Motzer RJ, Tannir NM, McDermott DF et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018 Apr 5;378(14):1277-1290. doi: 10.1056/NEJMoa1712126. Epub 2018 Mar 21.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Kidney Cancer. V.2.2017. Accessed at: on June 5, 2017.

Pili R, Kauffman E, Rodriguez R. Ch 82 - Cancer of the kidney. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 5th ed. Philadelphia, Pa: Elsevier: 2014.

Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443-2454.




Last Medical Review: August 1, 2017 Last Revised: August 1, 2017

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