Single-Cell Functional Proteomics Reveals Insights into Optimization of Radiation and Immunotherapy

Oncology has experienced a remarkable transformation in recent years due to the increased study and application of genomics and personalized medicine. Now, with more attention being placed on utilizing the patients’ own immune systems to eradicate cancer, radiation oncology is positioned to make a similar shift. As advances in molecular immunology are integrated with automation, radiation therapy (RT) will be ushered into an era of personalized multimodality systemic treatment.1

Though one of the most effective methods in providing local tumor control, with continuous improvements in patient-specific radiation planning and delivery, RT has the potential to be instrumental for systemic disease control as well.1 T cells activated by RT can exercise effects beyond local disease to enhance systemic control: when coupled with immunotherapy, the same RT techniques used for local control could convert tumors into in situ vaccines. In addition, advances in radiation planning and delivery may lead to more efficient patient-specific treatments, improved dosimetry, and faster delivery, allowing for simultaneous treatment of multiple lesions and sites. 1

As RT becomes more commonly used in systemic and local disease control, the principles of personalized medicine will help guide the treatment chosen for metastatic cancer. Patients with multiple sites, for example, may receive a low dose to all lesions or a high dose and low dose combined depending on the state of their immune system. Patients with weaker immune systems may be given cell therapy as well as RT, jumpstarting their immune cells while simultaneously attacking the cancer in multiple sites.

In a recent paper, published in the International Journal of Radiation Oncology, Biology, Physics, researchers evaluated  the efficacy of personalized medicine multimodality systemic treatment for patients with metastatic cancer. The use of low-dose radiation therapy was explored as a way to overcome the inhibitory tumor stroma, known for blocking tumor-infiltrating leukocytes (TILs) and immune cells from entering the tumor, and promote systemic immune responses.

Single-Cell Proteomics is Key to Selecting Optimal Radiation Dose

High-dose and low-dose RT are used differently—high-dose RT applies local control and immune activation in oligometastatic (contained to the singular site of origin) or polymetastatic disease, while low-dose RT stimulates distinct antitumor immune pathways and regulates the tumor stroma to improve T cell and TIL infiltration. To gain a better understanding of the efficacy of these treatments, researchers looked at both high and low dose RT as well as the integration of these techniques with emerging immune cell therapy. 1

The team used Isoplexis’ single-cell functional technology to “determine the polyfunctional strength index (PSI) of isolated cells after treatment with high- or low-dose RT. PSI is a measure of the percentage of individual cells that secrete two or more effector or regulatory soluble factors, multiplied by the intensity of such factors, and has been validated in the immunotherapy setting as a potential predictor of response.”1

The use of single-cell proteomics uncovered the importance of selecting radiation dose based on the intended immune cell stimulation. High-dose radiation stimulated cytotoxic T cell functionality, while low-dose radiation stimulated the activation of helper T cells, which can strengthen CD8þ T cells and help generate immune memory.1 Due to this imbalance of function between the different doses, combining both techniques offers a new focus of therapy that is central to the patients’ specific cancer, with their immune system and immune status central to the planning and execution of their therapy.

The study suggests that, when combined with immunotherapies, RT may be key to creating in situ vaccines that use the patients’ immune system to fight their specific cancer. The authors concluded that this approach will likely evolve over the next few years and is expected to expand the benefits of radiation to more patients as new immunotherapy options become integrated with radiation oncology.

Conclusion

Oncology therapeutics continue to make great strides thanks to the expanding knowledge gained from functional proteomics, genomics, and single-cell analysis. Radiation therapy is poised to make a similar shift, and with Isoplexis’ precision development and pathway monitoring, even more advancements are being made in this research field.  IsoPlexis’ technology detects the key intracellular pathways and functionality in tumor cells that can uncover critical and unseen targets in oncology, helping you understand the impacts of your therapies earlier in development, as well as mechanisms behind patient resistance in oncology research.2

Contact us today to learn how we can help accelerate cancer Immunology with functional Proteomics.

 

References

  1. Patel, Roshal R., et al. “Use of Multi-Site Radiation Therapy for Systemic Disease Control.” International Journal of Radiation Oncology, Biology, Physics. Vol 109:2, p 352-364. February 2021. DOI: https://doi.org/10.1016/j.ijrobp.2020.08.025
  2. Oncology: Single cell proteomics. IsoPlexis. https://isoplexis.com/research-areas/solid-tumor-oncology/.
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