Ranitidine Inhibition of Breast Tumor Growth Is B Cell Dependent and Associated With an Enhanced Antitumor Antibody Response
Bibliographic record
Abstract
Background: The histamine receptor 2 antagonist ranitidine is a commonly used, non-prescription, medication. It limits the development, growth and metastasis of breast cancers in mouse models of disease. In the current study, we examined the role of B cells in this response, the impact of ranitidine on the development of anti-tumor antibodies and subpopulations of natural killer cells using murine breast cancer models. Methods: Peripheral blood granulocyte populations were assessed in both E0771-GFP and 4T1 orthotopic tumor bearing mice by evaluation of stained blood smears. Antibody responses were assessed both in terms of the levels of anti-GFP antibodies detected by ELISA and also by antibody binding to the surface of tumor cells evaluated by flow cytometry. B cell and NK cell populations were examined in the draining lymph nodes and spleens of tumor bearing animals, by flow cytometry with and without ranitidine treatment. Results: Oral ranitidine treatment was not associated with changes in peripheral blood granulocyte populations in tumor-bearing mice. However, ranitidine treatment was associated with the development of enhanced anti-tumor antibody responses. This was not limited to the tumor setting since ranitidine treated mice immunized with ovalbumin also demonstrated increased IgG antibody responses. Analysis of B cell populations indicated that while B1 cell populations remained unchanged there was a significant decrease in B2 cells in the tumor draining inguinal lymph nodes. Notably, ranitidine did not significantly inhibit primary tumor growth in B cell-deficient animals. Examination of NK cell populations revealed a significant decrease in the proportion of intermediately functionally mature NK cells populations (CD27+CD11b-in ranitidine-treated tumor bearing mice compared with untreated tumor bearing controls. Conclusions: These data demonstrate an important role for B cells in the enhanced anti-tumor immune response that occurs in response to ranitidine treatment. Our findings are consistent with a model whereby ranitidine reduces tumor associated immune suppression allowing for the development of more effective anti-tumor responses mediated by B cells which may include the participation of NK cells. These data underline the importance of considering widely used histamine receptor antagonists as modulators of anti-tumor immunity to breast cancer.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".