Modeling a Wall of Flesh That Makes All The Difference in Cancer Immunology

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Immunotherapy In Essence

The same immunotherapy drug, at the same dose, for the same diagnosis, can cure one patient and do almost nothing for another. The difference may come down to a few microns of tissue standing between the drug and its target. 

Immunotherapy has been a rising treatment to cancer for decades: fundamentally, it trains the body to help recognize and attack cancer cells. According to the American Institute for Cancer Research, immunotherapy is now recognized as one of the five major types of cancer treatment, alongside surgery, radiation, chemotherapy, and targeted therapy.

Cancer immunotherapy is well-regarded due to its precision, resilience, and memory. Immunotherapy is highly workable, since the immune system adapts dynamically just as cancer does, making it applicable to many different types of cancer. Since the immune system is able to “remember” cancer cells, it can target the cancer if it ever returns in a patient, thus serving as a promising solution to cancer. Primary drawbacks of immunotherapy include its variability between each patient and its costly implications, such as one infusion for T-cell transfer therapy costing $373,000 on average. 

The reasons for immunotherapy’s effectiveness on some patients but not others is a research question being investigated today. One likely determining factor is the relationship between immunotherapy treatments and the body’s extracellular matrix (ECM). 

The extracellular matrix is a complex, webbed structure that exists outside of and between cells in all tissues and organs. It is a long, concealing maze, shielding tumors and other sites of interest. This structural barrier is a key reason as to why immunotherapy finds success in treating blood cancers but only works for 20% to 40% of patients with solid tumors. At a microscopic level, there is an interminable distance needed to be traveled through the ECM to a desired site of treatment. Navigating this may have less to do with decoding a tumor’s genetics than mapping the terrain around it. 

A Matter of Physics

Dr. Kolade Adebowale, assistant professor at UCSD in the Department of Bioengineering, seeks to understand the biophysics of cancer immunology in his research. Having been involved with cancer research since his undergraduate studies at Illinois Institute of Technology, Adebowale quickly realized a truth that “cancer is more than just cancer cells”, with one of the most fascinating non-cancer cells to him being immune cells. Driven by interest and dedication to understanding how immune cells work in cancers, Adebowale pursued a PhD at Stanford University and went into a postdoc at Harvard. 

“Some people think that the extracellular matrix is just a passive material that holds cells together, but there has been a systematic demonstration that this is not the case. The extracellular matrix is an active material that can not only provide structural support, but also instruct cells to do specific functions,” Adebowale explains. In other words, the ECM is an intricate labyrinth that tugs and interacts with cells: physical blockages as well as chemical and biological signals contribute to the path taken.   

Adebowale elucidates a main cause of cancer fatality: 90% of cancer deaths are estimated to be caused by the lethal “hike” that is metastasis. Metastasis is the process by which tumor or cancer cells move from their points of initiation to somewhere else, either in the same tissue or somewhere else in a distant tissue. “A critical process of hiking is the ability to move physically, and so if we can understand in greater detail how the cancer cells are moving, we can potentially stop them from moving, thereby improving patient outcomes.” 

How can the variable movements through this tricky wall of flesh be better understood? This traversal is what makes the difference between a treatment succeeding versus getting lost in the matrix of the body.

A Platform For Discovery: Gels and Their Surprising Uses

One method to map out the trajectory of a drug is observing its behavior in a simulated environment and noting its interactions with living cells. For in vitro tissue engineering, an out-of-body replication for the ECM is needed to sustain these biological experiments. The ECM features different textures throughout the body: in soft tissues such as lungs or brain, the ECM has the consistency of a hydrated jelly; in joints, ECM forms cartilage that is fibrous and tough. Within the softer frameworks, which usually surround more delicate regions, the consistency of the ECM feels much like a gel. Hydrogels, cross-linked polymer networks that act like a molecular net, have been designed for this purpose of mimicking the ECM.   

Dr. Reem Khojah, assistant professor at UCSD Bioengineering, teaches a graduate laboratory course on tissue engineering, BENG 277. Within the laboratory, students learn how to design different hydrogel mixtures and grow organoids embedded within these gels. 

“Cells exist within a complex environment that provides mechanical support, chemical support, and physical forces that regulate how tissue functions. The ECM of the tissue gives tissue their shape and structures. Chemical regulators switch biological factors on and off, and physical factors like fluid flow transport these chemical signals throughout the tissue.” Khojah says. 

In my experience auditing BENG 277, students engineered biomaterial scaffolds that provide structural support for organoids, which are living “mini organs” derived from stem cells. Student teams formed and tested different combinations of gels composed of alginate, Thiol-Modified Hyaluronan (HyStem), and Thiol-Modified Hyaluronan and gelatin (HyStem-C). Samples were then observed under the microscope and mechanically tested with a gel strength tester in order to compare results with real behaviors of the ECM. Over a period of several weeks, organoids were anchored within the experimental gels and their health was observed via monitoring of morphological and physical changes. Organoid media, a thin, pinkish liquid which serves as the nutrients for these cells, was administered through the hydrogels to the organoids in order to assess how the drug traveled through the gels. 

Building a replica of a living system using synthetic materials proposes a fascinating and reproducible pathway to understanding the immunotherapy problem. According to a study published in Chemical Engineering Journal, hydrogels can simulate the stress-relaxation properties of soft native tissues, allowing the cells to sense and respond to varying mechanical signals. This holds similar to the push and pull of the real extracellular matrix, and the complex layering of hydrogels enables disease modeling to expand outside of living bodies. By isolating the experiment into a curated petri dish with transparent gels, hikes can be watched closely in a controlled 3-D space. 

The next steps are to use organoids from specific patients to develop personalized treatments, which will bridge the gap between an effective and non-effective immunotherapy treatment. Instead of a generalized therapy, patients can receive infusions that are tailored to what will work for their bodies. Because these patient-derived organoids are grown and tested within hydrogels rather than inside the body, researchers can try multiple treatments with no risk to the patient. “One of the things I would love to do long term is to be able to grow human patients’ cancers essentially in organized models called organoids, and determine what therapies are going to be most effective for this patient,” Kolade Adebowale says. 

 “I don’t know if it can translate into a cure, but we’re hoping to translate into better, improved therapies. [...] We at least hope to be able to put the cancer in remission for a very long time.” †

Written by Staff Writer Selina Chen (syc021@ucsd.edu) 

Works Cited

American Cancer Society. "What Is Immunotherapy?" American Cancer Society, www.cancer.org/cancer/managing-cancer/treatment-types/immunotherapy.html. Accessed 27 June 2026.

Buntz, Brian. "With Prices Topping $4 Million, High Stakes Define Cell and Gene Therapy Landscape." Drug Discovery and Development, 26 Apr. 2024, www.drugdiscoverytrends.com/how-price-safety-and-efficacy-shape-the-cell-and-gene-therapy-landscape/.

Chen, Xiaohua, et al. "Hydrogels for Cancer Immunotherapy: Strategies From Construction to Application." MedComm, vol. 7, no. 2, 2 Feb. 2026, e70615, pmc.ncbi.nlm.nih.gov/articles/PMC12865231/. doi:10.1002/mco2.70615.

Dean, Barbara. "Immunotherapy for Cancer: How It Works, Benefits and What's Next." American Institute for Cancer Research, 11 Sept. 2025, www.aicr.org/resources/blog/immunotherapy-for-cancer-how-it-works-benefits-and-whats-next/.

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Mai, Zizhao, et al. "Modulating Extracellular Matrix Stiffness: A Strategic Approach to Boost Cancer Immunotherapy." Cell Death & Disease, vol. 15, no. 5, 1 May 2024, p. 307, pmc.ncbi.nlm.nih.gov/articles/PMC11063215/. doi:10.1038/s41419-024-06697-4.

Nelson, Roxanne. "How Much Does Immunotherapy Cost? Prices, Insurance, and Resources for Saving." GoodRx, updated 19 Sept. 2024, www.goodrx.com/drugs/biologics/resources-for-affording-immunotherapy.

Cover Image: “Hydrogel Scaffold”, David Nisbet, Monash University, via National Informal Stem Education Network. https://www.nisenet.org/catalog/scientific-image-hydrogel-scaffold