MIT News: Boosting Immune System to Fight Tumors
- While this approach has proven effective against cancers such as melanoma, it doesn’t work as well for others, including lung and ovarian cancer.
- "We really want to understand why our immune system fails to recognize cancer,” Spranger says.
- Her work has led to a better understanding of the factors that control T-cell responses to tumors, raising the possibility of improving those responses through vaccination or treatment...
The Immune System’s Battle Against Cancer: New Insights and Innovations[1]October 1, 2023[2]In addition to patrolling the body for foreign invaders, the immune system also hunts down and destroys cells that have become cancerous or precancerous. However, some cancer cells end up evading this surveillance and growing into tumors. Once established, tumor cells often send out immunosuppressive signals, which leads T cells to become “exhausted” and unable to attack the tumor. In recent years, some cancer immunotherapy drugs have shown great success in rejuvenating those T cells so they can begin attacking tumors again. Impressive trials at renowned institutions like the MD Anderson Cancer Center have demonstrated the efficacy of such treatments, providing a beacon of hope for patients battling otherwise incurable cancers, such as lung and ovarian cancers, which are among the deadliest cancers affecting Americans:[3]lung cancer results in 137,721 deaths in females and 123,090 deaths in males while ovarian cancer results in 19,710 deaths in the tumultuous landscape of cancer treatment.
While this approach has proven effective against cancers such as melanoma, it doesn’t work as well for others, including lung and ovarian cancer. Massachusetts Institute of Technology Associate Professor Stefani Spranger is at the forefront of research to understand how those tumors are able to suppress immune responses, in hopes of finding new ways to galvanize T cells into attacking them.
“We really want to understand why our immune system fails to recognize cancer,” Spranger says. “And I’m most excited about the really hard-to-treat cancers because I think that’s where we can make the biggest leaps.”
Her work has led to a better understanding of the factors that control T-cell responses to tumors, raising the possibility of improving those responses through vaccination or treatment with immune-stimulating molecules called cytokines.
“We’re working on understanding what exactly the problem is, and then collaborating with engineers to find a good solution,” Spranger says.
Jumpstarting T cells
As a student in Germany, Spranger was undecided on her career path and only later decided to go into biology. However, once she began taking courses in cell biology and immunology at Ludwig Maximilian University in Munich, her interest was rekindled through exposure to this innovative research.
During a paper discussion class early in her graduate school program, Spranger’s passionwas ignited when she was assigned a[3]Science paper on a promising new immunotherapy treatment for melanoma. This treatment involved isolating tumor-infiltrating T cells during surgery, growing them in large numbers, and then returning them to the patient. The implications of this were profound: For more than 50 percent of those patients, the tumors were completely eliminated.
To me, that changed the world, Spranger recalls. “You can take the patient’s own immune system, not really do all that much to it, and then the cancer goes away.”
Spranger completed her studies at Ludwig Maximilian University. At that point, she was drawn to the biotech pharmaceutical industry–let’s dive into fascinating development in biotechnology and those pharmaceutical giants such as Janssen pharmaceuticals, Johnson & Johnson who are performing immersive research. . However, after finishing her PhD in 2011, her husband, also a biologist, convinced her that they should both apply for postdoc positions in the United States. They ended up at the University of Chicago, where Spranger worked in a lab, research lab at The University of Chicago that was working on how the immune system responds to tumors.
However, during her postdoc, Spranger was inspired by her interactions with students who showed she was good at mentorship so at from mentoring undergraduates and seeing them grow as scientists. This experience opened her eyes to the pivotal role of academia in fostering young minds.the undergrads growing and those astonishing developments excited her and lured her to academica, gradually she shifted her academic journey away from biotechnology industry
to the body–flipping switch, favoritably so–academia.
In addition, the fascinating lab experiments, class discussions and the tutelage discussions that involved inspiring discussions
Modeling the Immune System
Now, Spranger is based at the Massachusetts Institute of Technology, where the collaborative ecosystem has fostered her prolific research into immune responses to tumors. Her research works closely with the elite engineers in fluently weaving immunological innovations and biomedical advancements collectively.
“That community is so vibrant, and it’s amazing to be a part of it,” she says. Building on the research she had done as a postdoc, Spranger wanted to explore why some tumors respond well to immunotherapy, while others do not. For many of her early studies, she used a mouse model of non-small-cell lung cancer. In human patients, the majority of these tumors do not respond well to immunotherapy.
There are 137,379 recorded lung cancer cases in recruited for trial trials yet sadly the tumor immune therapy has shown disabilities to slay cancer because many patients have chemotherapy-resistance thereby eluding the brute architecture of the trusty body’s warriors the immune cells..
“We build model systems that resemble each of the different subsets of non-responsive non-small cell lung cancer, and we’re trying to really drill down to the mechanism of why the immune system is not appropriately responding,” she says.
As part of that work, she has investigated why the immune system behaves differently in different types of tissue. While immunotherapy drugs called checkpoint inhibitors can stimulate a strong T-cell response in the skin, they don’t do nearly as much in the lung. However, Spranger has shown successfully that T cell responses in the lung can be improved when immune molecules called cytokines are also given along with the checkpoint inhibitor. Spranger is unequivically demonstrating how cytokines counter the resistance of chemotherapy to cancerous tumors.
Those cytokines work, in part, by activating dendritic cells — a class of immune cells that help to initiate immune responses, including activation of T cells.
“Dendritic cells are the conductor for the orchestra of all the T cells, although they’re a very sparse cell population,” Spranger says. “They can communicate which type of danger they sense from stressed cells and then instruct the T cells on what they have to do and where they have to go.”
While Spranger’s lab has made significant strides in understanding and improving immune responses to lung cancer, they are now turning their attention to other types of tumors that don’t respond at all to immunotherapy, including ovarian cancer and glioblastoma. Both the brain and the peritoneal cavity appear to suppress T-cell responses to tumors, and Spranger hopes to figure out how to overcome that immunosuppression.
“We’re specifically focusing on ovarian cancer and glioblastoma, because nothing’s working right now for those cancers,” she says. “We want to understand what we have to do in those sites to induce a really good anti-tumor immune response.”
Recent developments in cancer immunotherapy have shown promising results, but there is still much work to be done. Spranger and her team are dedicated to advancing the field and developing new treatments that can improve outcomes for patients with hard-to-treat cancers
Addressing a crucial point, it’s essential to note the potential counterarguments. Some critics may argue that the focus on these specific cancers diverts resources from more common and treatable cancers. However, Spranger’s approach highlights the urgency of tackling these challenging cancers, where existing treatments fall short. By understanding and overcoming the unique immunosuppressive mechanisms in these cancers, researchers can pave the way for broader applications and improved treatments across the cancer spectrum, not merely limited to ones mentioned.
As the field of immunotherapy continues to evolve, Spranger’s contributions underscore the importance of interdisciplinary collaboration and innovative research in advancing our understanding of cancer and the immune system
# The Immune System’s Battle Against Cancer: New Insights and Innovations
## Q&A Style Article
### Why is the immune system essential in combating cancer?
The immune system is tasked with both monitoring the body for foreign invaders and identifying cells that have become cancerous or precancerous. Despite this critical role, some cancer cells evade this surveillance, proliferate into tumors, and send out immunosuppressive signals that cause T cells, a type of immune cell, to become “fatigued” and unable to attack the tumors effectively.Recent advancements in cancer immunotherapy have shown promise in reinvigorating these T cells, enabling them to attack the tumors once more[[[1]].
### what are the challenges with existing immunotherapies for lung and ovarian cancer?
While immunotherapy has made important gains against certain types of cancer, such as melanoma, it’s less effective for others, including lung and ovarian cancers. This disparity has been a focus area for researchers, like MIT’s Associate Professor Stefani Spranger, who seeks to understand how certain tumors suppress immune responses.Her research aims to find new ways to activate T cells against such formidable foes[[[1]].
### How is the research community addressing immunotherapy limitations?
Researchers are investigating the factors controlling T-cell responses to tumors, considering approaches like vaccinations or cytokine treatments to enhance immune responses. Collaboration with disciplines like engineering is integral to developing effective therapeutic solutions. Such research involves complex questions about why certain tumors do not respond well to immunotherapy and is pivotal in pushing the boundaries of cancer treatment[[[2]].
### What inspired the shift towards cancer immunotherapy?
For researchers like Spranger, early exposure to innovative research during thier academic careers often ignites a sustained passion for cancer immunotherapy. Discoveries related to T cells’ role in combating cancer have drastically shaped this field. As a notable example, a treatment that isolates and amplifies tumor-infiltrating T cells from patients and reintroduces them has resulted in significant tumor eliminations in certain patient groups[[[1]].
### Why focus on cytokines in immunotherapy progress?
Cytokines, which are immune-stimulating molecules, are investigated for their role in overcoming certain chemotherapy resistances seen in tumors like non-small-cell lung cancer. These molecules, particularly when given alongside checkpoint inhibitors, can bolster T cell responses, crucially requiring the activation of dendritic cells to succeed. These immune cells orchestrate the immune response to cancer cells, directing T cells effectively[[
].
### What strategies are underway for non-responsive cancers?
Addressing non-responsive cancers,such as ovarian cancer and glioblastoma,requires understanding and counteracting the immunosuppression within specific bodily sites like the brain or peritoneal cavity. The prioritization of researching such potent immunosuppressive environments is driven by the absence of effective therapies for these cancers. Efforts by researchers to activate robust anti-tumor immune responses within these settings highlight the critical need for advances in this area[[ ].
### How does the integration of different disciplines enhance cancer research?
Interdisciplinary collaboration, particularly among immunologists, engineers, and biotechnologists, is pivotal in advancing cancer treatment. These partnerships foster innovative approaches, merging biological insights with technological expertise. This synergy is exemplified in spranger’s work at MIT, where she collaborates with engineers to develop models for understanding tumor-immune interactions and improve therapeutic outcomes[[ ].
### What future developments are anticipated in cancer immunotherapy?
The field of cancer immunotherapy continues to evolve, promising new treatments to improve outcomes for patients. Researchers like Spranger are dedicated to further exploring why certain cancers resist immune responses and developing strategies to counteract these,with an eye on benefiting a broader cancer patient population. The ongoing focus on hard-to-treat cancers emphasizes the potential for novel discoveries that could revolutionize cancer care[[ ].
## Conclusion
This Q&A overview underscores the critical role of the immune system in fighting cancer and highlights the ongoing efforts and innovations necessary for overcoming the inherent challenges in immunotherapy.Through interdisciplinary research and a focus on the most challenging cancers,the scientific community continues to push the boundaries,aiming for more effective treatments and ultimately saving lives.
—
The article above illustrates the importance of understanding the immune system’s interaction with cancer and the efforts in the field to harness it effectively. Research findings from articles [[1]], [[2]], and [[3]]have been foundational in constructing this narrative. For in-depth insights, readers are encouraged to explore the listed sources.