The Search for Immune-Specific Biomarkers Is in Full Swing

Howard L. Kaufman, MD, FACS and Ann W. Silk, MD
Published: Monday, May 04, 2015
Rutgers Cancer Institute of New JerseyHoward L. Kaufman, MD, FACS
Howard L. Kaufman,
Associate Director, Clinical Science
Chief Surgical Officer

Ann W. Silk, MD
Ann W. Silk, MD
Medical Oncologist

Rugters Cancer Institute of New Jersey
New Brunswick, NJStrategic Partners
An improved understanding of how the immune system recognizes and eradicates cancer cells, along with advances in drugs that effectively promote antitumor immune responses, is revolutionizing the field of cancer therapy. During the past four years, several randomized clinical trials have demonstrated significant improvements in both objective response rates and overall survival for several tumor immunotherapy agents.1

There are now an increasing number of immunotherapy agents available for the treatment of advanced cancers, including six FDA-approved drugs for melanoma (interferon, pegylated interferon, interleukin-2 [IL-2], ipilimumab, pembrolizumab, and nivolumab); two in renal cell carcinoma (interferon, IL-2); and one each in lung cancer (nivolumab) and prostate cancer (sipuleucel-T).

In contrast to targeted therapies that tend to mediate tumor regression quickly and in a large number of patients, immunotherapy tends to mediate tumor regression more slowly and in a smaller number of patients. Perhaps the most important difference, however, is that immunotherapy is often associated with durable responses and an associated improvement in overall survival. Thus, a major focus in the field has centered on identifying predictive biomarkers that might allow appropriate patient selection for immunotherapy.

The use of biomarkers to select appropriate drugs for individual patient treatment has been well established for genomic targeting. This is exemplified by the emergence of “precision medicine” programs throughout major academic centers and even in some community oncology practices. Such programs rely on genomic sequencing of a patient’s tumor to identify therapeutic approaches based on an analysis of mutated genes within an individual tumor.

In essence, specific genetic mutations, especially driver mutations that are known to maintain tumor growth, serve as predictive biomarkers that are used to guide therapeutic selection. Patients with certain cancer types, such as BRAF-mutated melanoma and ALK-rearranged non—small cell lung carcinoma, have a high likelihood of responding to targeted therapy. Targeted therapies have succeeded in improving overall survival when tested in patients known to have tumors with the specified mutations.

Tumor-Immune Interaction as Biomarker

Given that many patients may benefit from both targeted therapy and immunotherapy, the identification of predictive biomarkers for immunotherapy response has become an important priority for tumor immunotherapists.

Thus, we recently coined the term precision immunology to profile the tumor-immune system interaction within a particular patient and then select the best option for treatment from the widening array of tumor immunotherapy approaches.2 Although precision immunology is in its infancy, there are already tantalizing clues that we may be able to use information from the host antitumor immune response as a biomarker for cancer diagnosis, prognosis, and response to individual therapeutic approaches.

According to the immune surveillance hypothesis, single cells or clusters of cells with dysregulated growth are eliminated by the host immune system before they become clinically relevant cancers.3 As described by Schreiber et al, this process has been termed the cancer immunoediting concept and involves three discrete stages: elimination, equilibrium, and escape.4

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