"The immunotherapy ipilimumab (Yervoy, Bristol-Myers Squibb Company) works amazingly well in some patients, hardly at all in others. A groundbreaking study that used deep sequencing techniques offers some clues as to why.
"Ipilimumab, which is marketed for melanoma but is being explored in several other cancer types, including prostate cancer, acts as a checkpoint blocker by inhibiting cytotoxic T lymphocyte– associated antigen–4 (CTLA-4).
"Immune repertoire sequencing has confirmed that blocking CTLA-4 increased turnover and diversity of the T-cell repertoire in some patients with advanced prostate cancer or metastatic melanoma, but also showed that patients who survived longest maintained clones of high-frequency T-cells they had developed before starting treatment."
Editor's note: Ipilimumab is a drug that boosts a patient's own immune system to fight cancer. It works by activating immune system cells called T cells, some subtypes of which may then attack tumors. Ipilimumab works very well for some patients, but not for others. This study found that patients who had certain tumor-fighting T cell subtypes already present before ipilimumab treatment were more likely to respond well and survive longer, possibly because these cells were readily available to fight cancer upon activation. The study also found that ipilimumab may prompt the immune system to "re-shuffle" the body's T cell subtypes, allowing patients with only a small amount of tumor-fighting T cells to generate more. (This may explain why some patients take longer to respond to ipilimumab than others; their immune systems need more time to build up the right T cells.) Based on the results, doctors may be able to monitor a patient's T cell subtypes ("immune repertoire sequencing") to determine whether ipilimumab will work, or to keep tabs on the effectiveness of ongoing ipilimumab treatment.