Targeting intra-tumoral lactic acidosis in hepatocellular carcinoma: a long way to go

Finkel, Jemima; Tsochatzis, Emmanuel

doi:10.21037/jxym.2017.03.01

Cited by 1 publication

(1 citation statement)

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“…While BiCyclA is yet to be assessed in a clinical setting, each of the components of BiCyclA (cyclo, bicarb, ethanol, ethyl cellulose) are individually are already used clinically in many countries. Of note, translation of oral bicarb buffer therapy into humans has been controversial; however, a few small studies have demonstrated favorable results after intravenous bicarb delivery to tumors to improve response to trans-arterial chemoembolization (TACE) [ 37 , 38 ]. Our results corroborate their findings and demonstrate that ablation can be combined with pH-modulating therapies to improve the anti-tumor immune response.…”

Section: Discussionmentioning

confidence: 99%

Targeting Tumor Acidosis and Regulatory T Cells Unmasks Anti-Metastatic Potential of Local Tumor Ablation in Triple-Negative Breast Cancer

Nief

Gonzales

Chelales

et al. 2022

IJMS

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Triple-negative breast cancer (TNBC) is an immunologically heterogenous disease that lacks clinically actionable targets and is more likely to progress to metastatic disease than other types of breast cancer. Tumor ablation has been used to increase response rates to checkpoint inhibitors, which remain low for TNBC patients. We hypothesized that tumor ablation could produce an anti-tumor response without using checkpoint inhibitors if immunosuppression (i.e., Tregs, tumor acidosis) was subdued. Tumors were primed with sodium bicarbonate (200 mM p.o.) to reduce tumor acidosis and low-dose cyclophosphamide (100–200 mg/kg i.p.) to deplete regulatory T cells, as has been shown independently in previous studies. A novel injectable ablative was then used to necrose the tumor, release tumor antigens, and initiate an immune event that could create an abscopal effect. This combination of bicarbonate, cyclophosphamide, and ablation, called “BiCyclA”, was tested in three syngeneic models of TNBC: E0771 (C57BL/6), 67NR (BALB/c), and 4T1-Luc (BALB/c). In E0771 and 67NR, BiCyclA therapy significantly reduced tumor growth and cured 5/7 and 6/10 mice 50 days after treatment respectively. In the metastatic 4T1-Luc tumors, for which surgery and checkpoint inhibitors fail, BiCyclA cured 5/10 mice of primary tumors and lung metastases. Notably, CD4+ and CD8+ T cells were found to be crucial for the anti-metastatic response, and cured mice were able to resist tumor rechallenge, suggesting production of immune memory. Reduction of tumor acidity and regulatory T cells with ablation is a simple yet effective therapy for local and systemic tumor control with broad applicability as it is not limited by expensive supplies.

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Section: Discussionmentioning

confidence: 99%