Immunotherapy has transformed the treatment of different types of cancer by helping the immune system recognize and attack tumor cells. However, many of these therapies are administered intravenously, which means they circulate throughout the body before reaching the tumor. During this journey, they may also interact with healthy tissues and cause adverse effects in organs that were not the intended treatment target.
This challenge raises an important question: what would happen if immunotherapy were administered directly into the tumor?
A clinical study published in Frontiers in Immunology evaluated precisely this strategy. The researchers analyzed the safety and potential antitumor effects of different immunotherapies administered through CT-guided intratumoral injection. The study included 169 patients with advanced solid tumors and represents one of the largest clinical evaluations of this procedure across different cancer types.
What is intratumoral immunotherapy?
Intratumoral immunotherapy involves introducing a therapeutic agent directly into a tumor lesion using a needle. Instead of administering the medication into the bloodstream so that it travels throughout the body, the goal is to concentrate it at the site where the cancer is located.
This strategy could offer several advantages. The first is achieving a high concentration of the medication inside the tumor. The second is reducing unnecessary exposure to other organs. It may also be possible to use a lower total dose than the amount administered intravenously while producing a stronger effect within the tumor microenvironment.
The tumor microenvironment consists of cancer cells, blood vessels, immune cells, supporting tissue, and various chemical signals. Many tumors transform this environment into an immunosuppressive space, meaning a place where the body’s defenses lose effectiveness. Local administration of immunotherapy seeks to change these conditions and promote a more active immune response within the lesion.
The expectation is not limited to affecting the injected tumor. If immune cells are activated locally, they may circulate throughout the body and recognize cancerous lesions in other locations. This phenomenon is known as the abscopal effect, or a systemic response triggered by a local intervention. However, demonstrating that this effect occurs specifically because of intratumoral immunotherapy requires carefully controlled studies.
The importance of using imaging to guide the needle
Not all tumors are located close to the surface of the skin. Some lesions are found inside the lungs, liver, pancreas, abdomen, or near sensitive structures. For this reason, precision is essential.
In the study, the procedures were performed by experienced interventional physicians. Computed tomography made it possible to plan the needle trajectory, observe its position, and confirm that the tip reached the inside of the tumor. The needle size was selected based on the dimensions of the lesion and the distance between the tumor and the point where the needle entered the skin.
Once the needle was correctly positioned, the medication was administered inside the lesion. In large tumors, several needles could be used to improve treatment distribution. In addition, some agents were mixed with a small amount of diluted iodinated contrast, making it possible to visualize their distribution through CT imaging.
What treatments were administered?
The patients received different classes of immunotherapy. These included immune checkpoint inhibitors targeting PD-1, PD-L1, and CTLA-4. Some examples were pembrolizumab, nivolumab, sintilimab, atezolizumab, durvalumab, and ipilimumab.
The medications could be administered alone or in combination. The study also included patients treated with CAR-T cells delivered directly into the tumor.
The therapy selected was not identical for every patient. A multidisciplinary team considered information such as immunohistochemistry, genetic testing, previous treatments, and responses to earlier immunotherapies. For example, a patient who had not responded to an anti-PD-1 antibody could be considered for an anti-PD-L1 agent.
For immune checkpoint inhibitors, the intratumoral dose was standardized at half of the approved intravenous dose. Treatments were generally scheduled every three weeks and continued until disease progression, unacceptable toxicity, or the patient’s decision to withdraw.
Figure 1. Image guidance supports precise delivery of a lower drug dose directly into the tumor, helping increase local concentration while reducing systemic exposure.
Nearly 900 CT-guided procedures
The 169 patients underwent a total of 878 intratumoral injection procedures. Some received only one treatment, while others were treated repeatedly. In certain sessions, as many as five different lesions were injected.
The treated locations varied widely. The most common included the liver, abdominal cavity, lungs, subcutaneous tissue, retroperitoneum, osteoarticular and vertebral structures, head and neck, pelvis, and pancreas.
How safe was the strategy?
Safety was the primary objective of the study. The most frequently reported adverse effects were:
- Fever in 60.36% of patients
- Local pain at the puncture site in 54.44%
- Chills in 18.34%
- Vomiting in 14.79%
Most of these reactions were mild and resolved spontaneously within the first 24 hours. When symptoms became difficult to tolerate, symptomatic treatment was sufficient in most cases.
Fifteen patients, representing 8.88%, experienced grade 3 or 4 adverse events. Ten experienced grade 3 events, while five experienced grade 4 events. Severe complications included hypotension, immune-related rash, pneumonitis, shock, and respiratory failure.
An important finding was that no treatment-related deaths were recorded.
These results suggest that CT-guided intratumoral administration can be performed with a relatively low frequency of severe toxicities. However, the findings alone do not prove that it is safer than intravenous administration because the study did not include a contemporary comparison group receiving systemic therapy.
What happened to the tumors?
The researchers also evaluated tumor response through contrast-enhanced CT scans performed approximately every three weeks.
The overall results were:
4 patients achieved a complete response
15 experienced a partial response
142 maintained stable disease
8 showed disease progression
The objective response rate—which includes complete and partial responses—was 11.24%. The disease control rate—which includes complete response, partial response, and stable disease—was 95.27%.
Can a local treatment produce effects at distant sites?
One of the most interesting findings was that 36 patients, representing 21.30%, showed shrinkage or disappearance of lesions that had not been directly injected.
The article describes the case of a patient with lung cancer and a brain metastasis. The intratumoral injection was administered into the lung lesion, while the brain metastasis did not receive local treatment. Follow-up imaging showed progressive regression of the brain lesion over the following 90 days. The authors considered that this finding could be compatible with a systemic antitumor response generated after local therapy.
A case of prolonged response
The study also presents the follow-up of an older man with small cell lung cancer. After rapidly progressing during systemic immunotherapy, he began receiving intratumoral injections into a lesion in the right lung.
Between July 2020 and October 2024, he received 23 treatments. The tumor began to shrink around the fifth month and showed substantial regression by approximately the twenty-seventh month. The images on page 7 document the radiological evolution over approximately 50 months.
This case illustrates that some patients may experience prolonged responses. However, an individual case cannot predict what will happen in most patients.
A step toward more localized and personalized treatments
This study provides clinical evidence that CT-guided intratumoral immunotherapy is technically feasible for lesions located in different organs. It also shows that the procedure can be repeated and that, within this cohort, most adverse effects were mild.
The most relevant finding is not that this strategy has been proven to replace systemic immunotherapy. It has not. Its importance lies in demonstrating that different immunotherapeutic agents can be delivered directly into the tumor with a relatively low rate of severe complications, while producing preliminary signals of local disease control and possible responses at distant sites.
Main reference:
Ou Y, Zhang J, Tan H, He B, Li T, Liu M, Zhi C, Huang J, Li M, Zuo S, Shah NUH, Chen Y, Huang J, Chen D, Qin R, Li X, Lian H, Wu Q, Yang H and Zhang Z (2026) CT-guided intratumoral immunotherapy for advanced solid tumors: a prospective clinical study of safety and systemic antitumor effects. Front. Immunol. 17:1869154. doi: 10.3389/fimmu.2026.1869154
Other references:
Som, A., Rosenboom, J. G., Chandler, A., Sheth, R. A., & Wehrenberg-Klee, E. (2022). Image-guided intratumoral immunotherapy: Developing a clinically practical technology. Advanced drug delivery reviews, 189, 114505. https://doi.org/10.1016/j.addr.2022.114505
Champiat, S., Tselikas, L., Farhane, S., Raoult, T., Texier, M., Lanoy, E., Massard, C., Robert, C., Ammari, S., De Baère, T., & Marabelle, A. (2021). Intratumoral Immunotherapy: From Trial Design to Clinical Practice. Clinical cancer research : an official journal of the American Association for Cancer Research, 27(3), 665–679. https://doi.org/10.1158/1078-0432.CCR-20-0473
