Cannabinoids and the tumor immune microenvironment

The tumor microenvironment is a community of interacting cells

Cancer cells interact with blood vessels, connective tissue, fibroblasts and many kinds of immune cells. Together these components form the tumor microenvironment (TME). Its signals can help restrain a malignancy or, under different conditions, support growth and immune escape. Understanding a cannabinoid therefore requires understanding which cell receives the signal.

Why immunity can both restrain and assist tumors

Cytotoxic CD8 T cells and natural killer (NK) cells can identify and destroy abnormal cells. Yet tumors can release suppressive signals and recruit cells that diminish an effective immune response. Immune checkpoint therapies aim to restore certain anti-tumor responses. Any substance that changes immune signaling may have consequences that vary with tumor type and treatment.

Tumor-associated macrophages and CB2

Tumor-associated macrophages (TAMs) are highly adaptable. They are sometimes described using M1/M2 labels, but real tumor macrophages exist across changing states. Some can support angiogenesis, suppress T cells or assist invasion. CB2 is expressed by multiple immune-cell populations, so its activation in the TME can change several competing pathways.

An important counterexample: CB2 activation is not always beneficial

The Hebrew original cites experimental lung cancer settings where CB2 activation was associated with reduced CD8 and NK-cell activity and greater tumor growth. In a mouse glioblastoma model, CB2 activation was associated with faster tumor progression; blocking CB2 shifted macrophage and CD8-cell patterns toward an anti-tumor response. These are model-specific findings, not proof of the same effects in patients.

CBD can behave differently in another model

A 2025 experimental study discussed in the source examined HPV-related head and neck cancer. CBD was associated with tumor inhibition in immunocompetent mice, while the result was absent in immunodeficient mice. The researchers reported changes in infiltrating CD4/CD8 T cells, NK cells, B cells and macrophages. This suggests an immune-dependent mechanism in that model, not a clinical cancer therapy.

Why different results are not necessarily contradictory

THC is not CBD; CB1 is not CB2; blocking a receptor is not activating it. Tumors differ in their gene expression, treatment exposure and immune surroundings. A compound may suppress a harmful inflammatory process in one setting while suppressing useful tumor-killing immunity in another. Statements such as “cannabis strengthens the immune system” are therefore too broad.

Blood vessels and cancer-associated fibroblasts

Tumor angiogenesis is influenced by factors such as VEGF, while cancer-associated fibroblasts can supply extracellular matrix, growth factors and cytokines. Preclinical studies consider whether cannabinoid signaling affects these supportive networks. Observing a change in a marker or cultured cell is not equivalent to shrinking a tumor in a person.

What does antitumor activity mean?

A compound could theoretically affect tumor-cell division, cell death, migration, blood-vessel development or the ability of the immune system to recognize cancer. These are different outcomes that require different experiments. Results that look promising in one assay may fail to translate to clinical benefit.

Checkpoint immunotherapy raises a practical safety question

If a patient receives anti-PD-1 or anti-PD-L1 treatment, immune activation is central to the therapy. The Hebrew source notes observational signals that cannabis use might be associated with poorer outcomes in some groups, but disease severity and other factors may explain such associations. Neither blanket claims of harm nor claims of safety are justified. The treating team should know what cannabinoid products a patient uses.

Key conclusions

Precision research might one day compare tumor CB1/CB2 expression, CD8 infiltration and macrophage states to identify which cannabinoid pathways to stimulate or inhibit. For now, the strongest conclusion is that the tumor immune microenvironment makes the biology context-dependent. Animal and laboratory studies do not support replacing standard cancer therapy with cannabis.

Read original Hebrew article ↗

Scientific sources cited by the Hebrew original

1. Therapeutic targeting of the tumor microenvironment with cannabinoids and their analogs.
   Find this source ↗
2. Cannabinoids in immune system-related diseases: From bench to clinic. 2025.
   Find this source ↗
3. CB2 function and tumor-associated macrophages in glioblastoma.
   Find this source ↗
4. CBD modulation of the tumor immune microenvironment in HPV-associated head and neck cancer. 2025.
   Find this source ↗