Beyond Tumor Staging: Measuring Immune Status at Initial Diagnosis to Detect and Prevent Melanoma Recurrence
Abstract
For the majority of patients diagnosed with melanoma, surgery is the only therapy ever needed for cure. However, for reasons poorly understood, in about 1 of every 6 cases, the original melanoma can still spread through the body and be discovered in other organs months to years later. Once metastases are discovered, they can cause unwanted symptoms and increase chance of death from melanoma. Currently, predicting which cases will spread is not very precise which leads in some cases to patients being given too much treatment, while in other cases patients do not receive enough treatment. There is also currently no way to detect melanoma recurrence, and usually the metastases are only discovered once a patient is experiencing symptoms (e.g., bleeding from intestine lesions). The current treatment for preventing melanoma recurrence/metastasis after surgery involves adjuvant therapy with anti-programmed cell death protein 1 (anti-PD-1) inhibitors, which are prescribed to patients with American Joint Committee on Cancer (AJCC) stage IIB or higher. However, it is known that the majority of metastatic melanoma tumors (over 60%) are resistant to anti-PD-1 therapy. Moreover, treatment with anti-PD-1 therapy will elicit no benefit for the majority of patients who have excellent prognosis after surgery alone. Overall, this under- or overtreatment of melanoma patients is due to two primary deficiencies in the field: (1) our inability to accurately assess metastatic potential/risk of recurrence; and (2) our inability accurately detect recurrence. The current method to determine who is at risk for melanoma recurrence relies on factors about the tumor (e.g., tumor thickness or Breslow depth) while detection of recurrence is limited to physical exam. Melanoma has long been known to interact with the immune system. Indeed, a strong immune reaction is thought to be necessary to control melanoma. However, immune response to tumor is not currently measured in the clinic nor used to determine which melanoma are at risk for spreading. As a result, tumor staging too often underestimates the recurrence rate for the majority of patients in the U.S. who die of metastatic melanoma. Finally, there is currently no way to detect recurrence until symptoms (bleeding, pain) arise and only then is treatment given. There is a critical need for reliable methods of identifying patients at highest risk for melanoma recurrence and methods for detection of recurrence to improve treatment and survival rates in this patient population. This proposal addresses three FY22 MRP Focus Areas: (1) Develop prediction and surveillance tools for distinguishing patient populations at risk for additional primary melanomas, recurrence, and/or metastasis. (2) Identify how the tumor microenvironment (e.g., stromal, immune, microbiome) impacts tumor initiation, response to therapy, progression, recurrence, and/or dormancy; and (3) Delineate the molecular pathways that influence metastatic spread, recurrence, and/or dormancy. Preliminary work from our group shows that measuring a melanoma patient’s immune status at initial diagnosis can serve as an accurate and reliable method for assessing metastatic potential. Specifically, our group has preliminary data showing that: (1) B cell orientation and activation in tumor draining lymph nodes (TDLN) can distinguish patients at high risk for recurrence; and (2) immune function measured in blood and TDLN associates with host antitumor responses and tumor control. Furthermore, we have preliminary evidence showing that blood-based markers, including a novel test we are developing, can improve early detection of recurrence and monitor effectiveness of adjuvant therapy in patients with stage IIB-IIIC melanoma. Based on our preliminary data, we plan to test immune function in patients at initial melanoma diagnosis by studying B cells in TDLN, testing immune function in blood and TDLN, and collecting blood at multip
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310746
Entities
People
- Georgia Beasley
Organizations
- Duke University
- United States Army