According to preclinical research, City of Hope researchers have found that a type of immune cell, ILC2, in the human body known to be important for allergies and other immune responses can also attack the cancer.
The results of the study were published in Cell.
ILC2 immune cell that attacks cancer: here's how it works
This immune cell, which belongs to cells called human innate lymphoid cells type 2 (ILC2), can be expanded outside the body and applied in greater numbers to overwhelm a tumor's defenses and eliminate malignant cells in mouse models of cancer .
“The City of Hope team has identified human ILC2 cells as a new cell family member capable of directly killing all types of cancer, including blood cancers and solid tumors,” said Jianhua Yu, Ph.D. , professor of the Department. of Hematology and Hematopoietic Cell Transplantation at the City of Hope and senior author of the study.
“In the future, this immune cell could be produced, preserved by freezing and then administered to patients. Unlike T cell-based therapies such as CAR T cells, which require the use of the patient's own cells due to their specific characteristics, ILC2s could originate from healthy donors, which present a distinct potential therapeutic approach as an allogeneic product and “ off-the-shelf”.”
In previous research focused on mouse cells, ILC2s had not consistently shown promise when tested for their cancer-killing abilities.
However, in City of Hope's highly translational labs, researchers prioritized examining human cells and found that human ILC2s do not function the same way as mouse ILC2s.
“Mice are typically reliable models for predicting human immunity, so it was a real surprise in the field to find that human ILC2s function as direct cancer killers while their mouse counterparts do not,” said Michael Caligiuri, MD, co-author of the study. senior author of the study and also a City of Hope professor in the Department of Hematology and Hematopoietic Cell Transplantation. “It's remarkable that something evolved so distinctly from mouse to man.”
To test human ILC2s, Yu and the team first isolated the cells from a blood sample. So, they developed a new platform that in four weeks can expand the ILC2s collected from the body by 2,000-fold.
They then injected these expanded cells externally into transplanted mice with human acute myeloid leukemia (AML) or solid tumors, including pancreatic cancer, lung cancer, and glioblastoma. The results showed that this cell population could kill these tumors through a previously unknown cancer-killing mechanism.
“Convincing and direct evidence appeared when we directly put an ILC2 and a tumor cell together and found that the tumor cell died, but the cell survived,” Yu explained. “This shows that the immune cells directly killed the tumor cell in the absence of any other cells.”
Yu noted that ILC2s do not need to come from the cancer patient's own cells, meaning that in the future there may be the possibility of harvesting and freezing immune cells from healthy donors for the treatment options in question.
Yu and Caligiuri have been studying a different type of cancer killer called natural killer cells, or NK cells, for decades. In fact, Yu is the founding director of the natural killer cell biology research program at City of Hope, a national leader in the field.
Yu and Caligiuri said that immune cells now represent a new member of the family of cytotoxic immune effector cells, along with NK cells and CD8+ T cells, which help the body fight cancer. They're excited to see how researchers might be able to harness the collective power of these different killer cells to better fight other diseases, too.
Yu and Caligiuri caution that because they are still in the early stages of understanding the anticancer functions of ILC2s, many questions remain. However, they intend to continue working with their collaborators to understand and learn more about human immune cells now that they know the cells are killers.
“Our goal is to really expand the applications of these findings, potentially beyond cancer treatments,” Yu said, noting that ILC2s could also work against viruses like COVID-19. “Additionally, we are working to translate our discovery into tangible clinical benefits.
The team has already overcome at least one hurdle in bringing ILC2s to clinical trials, and that is having enough product to test. ILC2s are rare in the body, Caligiuri said, and are found in greater numbers in the lungs, intestines and skin. The team has a platform to help them grow quickly.
“We need to be able to expand these cells for human clinical trials, and one of the interesting things is that we're on the right track,” Caligiuri said. “At City of Hope, we have the advantage of access to our Good Manufacturing Practices compliant facilities that can produce cells for us and accelerate discoveries in clinical trials.”
The therapeutic potential of human innate lymphoid cell type 2 (ILC2) has been underexplored. Although not observed in mouse immune cells, human immune cells have been found to secrete granzyme B (GZMB) and directly lyse tumor cells by inducing pyroptosis and/or apoptosis, which is governed by a DNAM-1− interaction CD112/CD155 inactivating the negative regulator FOXO1.
Over time, high-density surface expression of CD155 in acute myeloid leukemia cells impairs DNAM-1 and GZMB expression, thus enabling immune evasion. We describe a robust platform capable of up to 2,000-fold expansion of human ILC2s within 4 weeks, whose molecular and cellular profiles were validated by single-cell RNA sequencing. In both leukemia and solid tumor models, exogenously administered expanded immune cells show significant antitumor effects in vivo.
The study team also included l
ead authors Zhenlong Li, Rui Ma, and Hejun Tang from the Yu and Caligiuri labs, as well as David Artis, Ph.D., Michael Kors Professor of Immunology and director of the Jill Roberts Institute for Inflammatory Bowel Disease. He researches at Weill Cornell Medicine.
In Italy, according to the ISS Epicenter: “In 2022, in Italy, there are an estimated 390,700 new cancer diagnoses (in 2020 there were 376,600), 205,000 in men and 185,700 in women.
The most frequently diagnosed cancer in 2022 is breast cancer (55,700 cases, +0.5% compared to 2020), followed by colorectal cancer (48,100, +1.5% in men and +1.6% in women). women), lung (43,900, +1.6% in men and +3.6% in women), prostate (40,500, +1.5%) and bladder (29,200, +1.7% in men and +1, 0% in women).
These are the main data that emerge from the report “Cancer numbers in Italy 2022” which describes the aspects relating to the diagnosis and treatment of cancers, underlining the importance of prevention through combating unhealthy lifestyles and adhering to screening , thanks to the work of the Italian Association of Medical Oncology (AIOM), the Italian Association of Tumor Registries (AIRTUM), the AIOM Foundation, the National Screening Observatory (ONS), the PASSI (Progressi delle Aziende Sanitarie per la Health in Italy) and PASSI d'Argento and the Italian Society of Pathological Anatomy and Diagnostic Cytology (SIAPEC-IAP).
Chronic non-communicable diseases (NCDs), in particular cardiovascular diseases, diabetes, cancer, chronic respiratory diseases and mental health disorders, are responsible for approximately 90% of deaths in the WHO European Region but, like behavioral risk factors responsible for their onset (use of tobacco and alcohol, unhealthy diet and insufficient physical activity), can be prevented. The process of preventing MCNTs is a multifaceted and complex public health issue, which a “one-size-fits-all” approach cannot effectively address.
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