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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Melanoma
• Intervention / Treatment: Other: High-performance liquid chromatography-tandem mass spectrometry assays

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 Type: Observational
• Enrollment (Estimated): 90

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Description of Population to be Enrolled:

Patients who are either chronic cannabis/cannabinoid users (use >1 time/week for >3 months of any cannabinoid product, with ingestion via edibles, smoking, or vaping) and non-users for the last year who are scheduled to be seen in a clinic at the University of Colorado Cancer Center will be approached for enrollment and informed consent. Enrollment will be limited to stage Ib and II to decrease patient heterogeneity and since higher TIL grade has been associated with earlier stage melanomas13, thus maximizing the potential to observe an effect. Biopsy specimens must be obtained within 4 weeks of study enrollment to ensure blood specimens are reflective of when biopsy specimens were obtained.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Chronic Cannabinoid Users; Ib or II Melanoma patients who are chronic cannabinoid users	Other: High-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
Non-users; Ib or II Melanoma patients non cannabinoid users	Other: High-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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Grade of TIL in melanoma biopsy	Hematoxylin and eosin slide assessment	24 Months
Composition of TILs within melanoma biopsy specimens	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	24 Months

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: Cancer League of Colorado
• Investigators: Principal Investigator: Camille Stewart, MD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): August 31, 2024

Study Registration Dates

• First Submitted: August 25, 2022
• First Submitted That Met QC Criteria: August 25, 2022
• First Posted (Actual): August 29, 2022

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma
• Other Study ID Numbers: 22-1132

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No