Evaluating the Effects of Cannabis Use and Circulating Cannabinoids on Tumor Infiltrating Lymphocytes in Malignant Melanoma

Active, not recruiting

• Conditions: Melanoma
• Interventions: Other: High-performance liquid chromatography-tandem mass spectrometry assays

• Registration Number: NCT05520294
• Lead Sponsor: University of Colorado, Denver

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.

Study Timeline

• Study First Submitted: 2022-08-25
• Study First Submitted QC: 2022-08-25
• Study First Posted: 2022-08-29
• Study Start: 2022-09-01
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-15
• Last Update Posted: 2024-04-17
• Primary Completion: 2024-08-31
• Study Completion: 2024-08-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 90

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)

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Exclusion Criteria

• Patients unwilling or unable to provide informed consent

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Chronic Cannabinoid Users	High-performance liquid chromatography-tandem mass spectrometry assays	Ib or II Melanoma patients who are chronic cannabinoid users
Non-users	High-performance liquid chromatography-tandem mass spectrometry assays	Ib or II Melanoma patients non cannabinoid users

Primary Outcome Measures

Name	Time	Method
Grade of TIL in melanoma biopsy	24 Months	Hematoxylin and eosin slide assessment
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

Trial Locations

Locations (1)

University of Colorado Denver; 🇺🇸 Aurora, Colorado, United States