Melanoma
Conditions
Brief summary
The goal of this proposal is to determine how cannabinoid use affects the tumor immune microenvironment (TME) of melanoma by correlating TILs with reported cannabinoid use and circulating plasma cannabinoids. The central hypothesis is that cannabinoid use decreases TILs in melanoma in a dose-dependent fashion. This is important because cannabinoid-driven TME changes in melanoma may alter patient outcomes mediated by TILs and response to standard of care ICI treatments.
Detailed description
Specific Aim 1.Assess how systemic cannabinoids remodel tumor infiltrating lymphocytes (TILs) within the melanoma tumor microenvironment. We hypothesize that decreased grade of TILs and exhaustive differentiation of T cells in melanoma are associated with lower cannabinoid receptor (CB1/CB2) expression and higher levels of systemic exogenous cannabinoids. Aim 1a.) Correlate plasma levels of cannabinoids with TIL grade. Aim 1b.) Correlate plasma levels of cannabinoids with TIL T cell immunohistochemical markers of exhaustion. Aim 1c.) Correlate plasma levels of cannabinoids to TIL CB1/CB2 expression. Specific Aim 2. Determine the relationship between peripheral T cell activation and circulating cannabinoid levels in patients with melanoma. We hypothesize that the phenotypic activation of peripheral T cells is inversely associated with increased plasma levels of systemic exogenous cannabinoids. Aim 2a.) Immunophenotype peripheral T cells from patients with melanoma. Aim 2b.) Correlate plasma levels of cannabinoids with peripheral T cell phenotypic activation.
Interventions
OTHERHigh-performance liquid chromatography-tandem mass spectrometry assays
Paraffin blocks will be requested for slide creation, and at least 12 mL of whole blood will be collected in 2 green top tubes, centrifuged, and plasma transferred for storage at -80 C until further processing
Sponsors
Cancer League of Colorado
University of Colorado, Denver
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
21 Years to 100 Years
Inclusion criteria
* Biopsy proven melanoma, any stage * Biopsy obtained within 4 weeks of anticipated enrollment * Patients \>21 years old * Report no cannabis use in the last year or chronic cannabis use (at least weekly use for 3 months or more)
Exclusion criteria
* Patients unwilling or unable to provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composition of TILs within melanoma biopsy specimens | 24 Months | Stains for TIL markers such as CD3, CD4, CD8, CD20, CD45RO, and FoxP3; T cell function IHC stains include: TOX, PD1, TIGIT, LAG3; melanoma specific marker SOX10 |
| Grade of TIL in melanoma biopsy | 24 Months | Hematoxylin and eosin slide assessment |
Countries
United States
Outcome results
None listed