Urologic Oncology: Seminars and Original Investigations
Seminar ArticleThe requirement for immune infiltration and organization in the tumor microenvironment for successful immunotherapy in prostate cancer
Introduction
Prostate cancer is the most common cancer diagnosis made in men today, and while surgery, radiation therapy, and expectant management strategies boast encouraging survival outlooks (with the 10-year risk of death from prostate cancer ranging from 3% to 18%, depending on risk group), therapeutic advances are still needed, especially for metastatic and hormone refractory patients [1,2]. Accordingly, there is hope that immunotherapy could fill this space—to be an effective therapeutic option for castrate resistant disease—or even become an earlier option, perhaps mitigating the undesired side effects of currently employed therapies. Here, we will review the successes and failures of using immunotherapy to treat prostate cancer. We discuss the mechanisms associated with immunotherapy response in other cancers and why prostate cancer may be more refractory to this approach.
Section snippets
Lessons and successes in prostate cancer immunotherapy
Since the Food and Drug Administration (FDA) approval of Sipuleucel-T for prostate cancer and of immune checkpoint therapies for melanoma, trials of immunotherapies have proliferated across a multitude of tumor types. The greatest success of immune checkpoint therapies was found in densely immune-infiltrated "hot" tumors, such as melanoma [3,4]. However, the trials conducted in immunologically "cold" (i.e., poorly immune infiltrated) tumors, such as prostate cancer, did not match the impressive
The composition of the immune microenvironment is prognostically valuable and functionally important
The tumor microenvironment (TME) includes numerous immune cell subsets, which are crucial in the antitumor immune response. Depending on the organization, location, and phenotype of the cells, they can either promote or impede the antitumor immune response (Fig. 1). In order to understand how the immune system is responding to different tumors, the cell populations must be analyzed and studied in order to understand the way these populations interact. The fundamental cell populations in the
Organization in the immune microenvironment
The association between tumor T-cell infiltration and improved survival and response to immunotherapy has resulted in the categorization of various tumors as either immunologically ‘hot’ or ‘cold.’ In addition, others have further delineated phenotypic categories of immune infiltration—immune-inflamed, immune-excluded, and immune-desert—in attempts to explain the variation seen clinical behavior [86]. Immune-inflamed tumors are generally thought to carry a positive prognosis, while
Future perspective
Here we have reviewed the use of immunotherapy in prostate cancer and the mechanisms that support responses to immunotherapy. Additionally, we have specified potential explanations for why immunotherapy has delivered lower response rates than in some other cancers. Based on the evidence presented here, it is clear that immune infiltration and organization in the TME—such as in the formation of TLS—plays an important role in antitumor immunity and in the response to immunotherapy. Specifically,
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