Potential therapy may boost chemoimmunotherapy response in bladder cancer (Adding cheap celecoxib allows T-cells to enter tumors)

Medical Xpress / Cedars-Sinai Medical Center / Nature Communications ^ | Mar. 28, 2022 | Fotis Nikolo, Ph.D. et al

[ConservativeMind]

Adding an anti-inflammatory medication to immunotherapy and standard chemotherapy drugs may provide long-term suppression of aggressive bladder tumor growth, according to a proof-of-concept study.

The researchers' previous work, led by Keith Syson Chan, Ph.D. found that the combined use of the chemotherapy drugs gemcitabine and cisplatin is unable to activate a patient's own immune response to cancer. They also found that chemotherapy prompts the overwhelming release of an inhibitory signal, or brake, that suppresses an immune response by counteracting "go" signals. When the investigators added the anti-inflammatory drug celecoxib to gemcitabine to remove the brake, they were able to shift the balance toward the "go" signals, improving the immune response in laboratory mice.

Building on those findings, the researchers discovered a mechanism that may drive the immune-dampening effect of chemotherapy and determined how to counteract it, therefore activating a longer-lasting immune response.

The researchers may have discovered why the combination of chemotherapy and immunotherapy often fails. In their current study, the investigators found that chemotherapy induced a remarkable release of prostaglandin E2, a bioactive lipid associated with inflammation and cancer. Called an inhibitory damage-associated molecular pattern, or iDAMP, prostaglandin E2 blocks dendritic cells from maturing and fighting cancer, explained Kazukuni Hayashi, Ph.D.

To counteract that effect, the researchers added to the chemoimmunotherapy the drug celecoxib. The anti-inflammatory medication targets the protein COX-2, which promotes the release of prostaglandin E2, Hayashi explained. This drug combination allows killer T cells to infiltrate the tumor core and kill the tumor cells.

"The addition of the celecoxib not only worked well with chemotherapy, it also sensitized bladder tumors toward chemoimmunotherapy, providing a long-lasting response," Hayashi said.

Next, the researchers plan to test the efficacy of the new treatment in colon and pancreatic cancer.

[ConservativeMind]

This would seem a no-brainer to add when taking chemo for certain cancers.

[ConservativeMind]

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[ought-six]

I’m a bladder cancer survivor. I had surgery, than chemo (with mytomycin) and intovesical immunotherapy (with BCG). I returned about two years later for another surgery wherein about one-third of my bladder was removed. That was almost 13 years ago.

[ifinnegan]

Celecoxib is Celebrex for those who don’t know.

Celecoxib may have direct anti-tumor effects.