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2023 Society of Urologic Oncology (SUO) – PCF Young Investigator Award

Defining Modifiable Components of the Immune Microenvironment in Patients with Prostate Cancer Nodal Metastases

Christopher Gaffney, MD
Memorial Sloan Kettering Cancer Center (MSKCC)

Mentors: Howard Scher, David Knorr, Behfar Ehdaie

Description:

  • Lymph nodes are small structures located throughout the body that help to initiate immune responses against cancer and infections. Prostate cancer commonly spreads to the lymph nodes, increasing the risk for distant metastases and death from prostate cancer.
  • Lymph nodes have an important role generating anti-tumor immunity which is increasingly important with the development of immunotherapies that activate the immune system against cancer.
  • However, the types of immune cells, their locations within the immune microenvironment, and their interactions with other immune cells in the lymph nodes of patients with prostate cancer lymph node metastases is unclear.
  • Dr. Christopher Gaffney is studying the biology of lymph nodes with prostate cancer metastases and their role in responses to androgen deprivation therapy (ADT) and a novel immunotherapy.
  • In this project, Dr. Gaffney and team will investigate the immune microenvironment of lymph nodes with prostate cancer metastases from patients who underwent surgery to remove the prostate and nearby involved lymph nodes to discover if the immune system appears suppressed within these lymph nodes.
  • ADT is hypothesized to enhance anti-tumor immunity by activating immune cells. Lymph node samples from patients who were treated with ADT prior to surgery will be studied to determine the impact of ADT on immune features and functions.
  • The team developed a clinical trial testing ADT in combination with a novel immunotherapy, anti-CD40, which is hypothesized to further activate immune responses against cancer. As a part of this project, the efficacy of this combination will be investigated in samples from a subgroup of patients with node-positive prostate cancer, to determine whether and how ADT + anti-CD40 modifies the immune microenvironment.
  • If successful, this project provide a comprehensive description of the immune microenvironment of lymph nodes with prostate cancer metastases, and determine how they are impacted by ADT alone or with immunotherapy. This information may be used to define aspects of the immune microenvironment that are modifiable with new classes of immunotherapies.

What this means to patients: Prostate cancer commonly metastasizes to lymph nodes, an event associated with distant spread and death from disease. These lymph nodes are immune organs that are hypothesized to be immunosuppressed in patients with cancer. Dr. Gaffney and team will comprehensively profile prostate cancer-infiltrated lymph nodes from patients and determine how immune features are changed by treatment with ADT alone or in combination with a novel immunotherapy, anti-CD40. These studies will provide critical insights into the immune mechanisms underlying prostate cancer progression and inform the development of novel therapeutic strategies.