Studies Finds New Immunotherapy Pathway to Prevent Breast Cancer, Gives Treatment Potential

Researchers from Massachusetts General Hospital identify a new immunotherapy pathway that acts against breast cancer Illustration - Mark Kostich/Shutterstock

A study by Massachusetts General Hospital has identified a previously unknown immune system mechanism underlying breast cancer prevention, creating potential for future immunotherapy.

The study found T helper 2 cells (Th2)—a type of regulatory immune cell—can “directly block spontaneous breast carcinogenesis [from becoming cancerous]” by regulating cancers cell to become unable to differentiate, according to lead author Dr. Shawn Demehri.

Though previous research showed that Th2 took part in cancer growth and proliferation rather than prevention, Demehri’s 2016 work showed that a specific messenger molecule in the immune system, called thymic stromal lymphopoietin (TSLP) is able to activate Th2 attack against breast cancer cells.

The study that Th2 cells could force the breast cancer cells to grow into terminal proliferation stages; a stage where cells would no longer be able to divide and proliferate, leading to eventual cell death as the cell ages.

“The Th2 cells force the cancer cells to go back to their original programming of making a breast gland that has no potential for growth or metastasis,” he said.

Once the Th2 cells are stimulated by the TSLP to enter breast cancer tumor masses, they will also release chemical messages that directly act on tumor cells, changing the tumor cells from high-grade to low-grade breast cancer cells.

High-grade cancer cells have a high risk of proliferation and metastasis—being able to spread to other sites to cause secondary tumors elsewhere—whereas low-grade tumors resemble normal cells and are slower growing and less likely to spread to other places, thereby making them easier to treat.

The breast cancer cells are induced to become low-grade cells. Though may look similar to normal breast gland cells, they are not entirely the same, instead forming tissues that are lumpy to the touch.

Th2 cells are “upstream activators” of the adaptive immune response, meaning that they regulate and control immune response against a targeted pathogen.

This makes them better targets for immunotherapy as compared to conventional immunotherapy that targeted the cytotoxic T cells (Tc) that engage in close combat with cancer cells rather than regulating the entire process, as Th2 cells can regulate the response of the Tc cells, mounting a more “robust antitumor immune response.”

Additionally, Th2 cells can turn “cold” tumors into “hot” tumors. “Cold” tumor cells that are not recognized and attacked by Tc cells due to the cancer cells being surrounded with other immune cells that suppress immune attack, however, Th2 cells can regulate Tc cells with immune messages, turning the tumors into “hot” ones.

Giving options for future treatments coming out of the study, the authors wrote calcipotriol, a molecule that leads to production of TSLP are “safe and accessible agents for breast cancer immunoprevention” though other ways of inducing TSLP in the body is being considered with one option given as administering mRNA of TSLP.

Whilst more research into the interaction between TSLP and Th2 is still needed, the researchers are confident that “inducing Th2 cell immunity in the breast can be readily translated into improved clinical outcomes for early and late breast cancer patients.”

Demehri and his colleague wrote that their “findings establish a previously unrecognized mode of immunity against early malignant [cancerous] transformation,” regulated by Th2 cells.

The authors say that their findings highlight the “importance of the immune activating signals” such as TSLP, which serve as early initiators of immunity against tumors and can be regulated through therapy for “cancer immunoprevention and treatment.”