Researchers Boost Cancer-Killing Immune Cells with Specific Signaling for Precise Tumor Attacks

Researchers at the National Cancer Institute announced on Monday that they genetically engineered myeloid cells to deliver interleukin-12 directly to premetastatic tumor sites in mouse models. According to Dr. Kaplan, this targeted approach activated cancer-killing immune cells, significantly reducing lung metastases and extending survival in treated mice.

The genetically engineered myeloid cells, termed GEMys, were designed to deliver interleukin-12 (IL-12) specifically to premetastatic niches, or sites where tumors are likely to spread, according to researchers at the National Cancer Institute (NCI). Myeloid cells naturally migrate to tumors and metastatic areas, which made them suitable vehicles for targeted cytokine delivery, officials said. Treated mice also exhibited notably longer survival, according to Dr. Kaplan, who described the approach as a “change in the conversation” by effectively activating cancer-killing immune cells.

In mouse models of rhabdomyosarcoma, a type of soft tissue cancer, treatment with GEMys led to a significant reduction in lung metastases and muscle tumors compared with controls receiving nonengineered cells.

The study builds on a growing body of research aimed at enhancing immune responses against cancer through precise cellular and molecular interventions. For example, a January 8, 2026, study published in Nature Communications by researchers at the University of Southampton introduced multi-pronged antibodies targeting the CD27 receptor on T cells. Led by Professor Aymen Al-Shamkhani at the Centre for Cancer Immunology, the antibodies were engineered with four binding arms to cluster CD27 receptors and recruit additional immune cells, thereby amplifying T cell activation. The team reported that these antibodies outperformed traditional Y-shaped antibodies in activating CD8+ T cells in both mouse models and human cell cultures.

Additional advances include a November 17 study published in Nature Immunology by Weill Cornell Medicine researchers exploring the role of CD47-thrombospondin-1 (TSP-1) signaling in T cell exhaustion. Dr. Chien-Huan Weng and colleagues found that tumors exploit CD47 on T cells to induce exhaustion, which impairs immune function. The study demonstrated that a peptide called TAX2 disrupts the CD47-TSP-1 interaction, preserving T cell activity. In melanoma and colorectal cancer mouse models, TAX2 slowed tumor progression and showed synergy with PD-1 checkpoint immunotherapy in colorectal tumors, officials said.

At Stanford University, a March 2026 study engineered natural killer (NK) and T cells to express the receptor GPR183, which senses oxidized cholesterol metabolites produced by tumors. According to Livnat Jerby, PhD, this modification enhanced immune cell migration and infiltration in breast and ovarian cancer mouse models. The researchers reported that chimeric antigen receptor (CAR) NK and CAR-T cells expressing GPR183 improved tumor control and prolonged survival in treated mice. Jerby described the approach as guiding immune cells to tumors by “following the yellow brick road” of cancer metabolites.

Researchers at MIT and Stanford also developed multifunctional proteins called AbLecs that combine lectins and antibodies to block glycan-based immune checkpoints. These proteins target sialic acid glycans on cancer cells, preventing Siglec receptors on macrophages and NK cells from inhibiting immune responses. Jessica Stark, who led the development of AbLecs, reported that in a lung metastasis mouse model expressing human receptors, AbLecs reduced metastases more effectively than trastuzumab, a commonly used antibody therapy. Laboratory tests showed that AbLecs reprogrammed immune cells to destroy cancer cells more efficiently.

Other notable research includes a September 2025 study from Johns Hopkins University that focused on converting immune-cold tumors, which typically do not respond to immunotherapy, into immune-hot tumors capable of eliciting robust B cell and T cell responses. The study introduced a novel mechanism to boost immune responsiveness within the tumor microenvironment, potentially broadening the efficacy of immunotherapies, according to official releases from the institution.

Finally, a study from Fox Chase Cancer Center revealed a mechanism by which reawakening endogenous retroviral elements within tumors can mimic viral infection signals, prompting the immune system to attack cancer cells. This approach, described by lead researcher Balachandran, tricks the immune system into recognizing tumors as infected tissue, thereby stimulating an immune response. The findings suggest a new strategy for activating immunity against cancer by harnessing hidden viral elements.

Together, these studies reflect a multifaceted effort across institutions to harness and enhance the immune system’s ability to target cancer more precisely and effectively. Researchers continue to explore combinations of these approaches and their potential translation into human clinical trials.