Advancing Immunology Therapy: Early Prediction of Skin Cancer Patients’ Chances of Responding to Treatment and Trials on Prednisone and Sirolimus for Kidney Transplant Recipients

Reading time: 5 minutes

Joycelyn Ghansah, MA, MPH

Active treatments like immunotherapy are used for various cancers, including melanoma, commonly known as skin cancer. Unfortunately, only about half of the patients respond to this type of treatment. Current research focuses on early prediction of skin cancers and identifying which patients are likely to respond positively to immunotherapy. Additionally, new trials are examining how immunology therapy, supported by immune suppressants like prednisone, can help kidney transplant patients who develop unresectable or metastatic skin cancer.

A recent study has found that a specific type of immune cell, Vd1-gd T cells, can help predict which patients are more likely to respond favorably to immunotherapy treatments.

As most clinicians and researchers recognize, selecting the most effective treatment often involves a trial-and-error approach. Immunotherapy can be a lifeline for skin cancer patients, especially those with advanced melanoma.  

Researchers from The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins are conducting a Phase II trial to investigate the use of immunotherapy for the treatment of unresectable or metastatic cutaneous (skin) cancer in kidney transplant recipients. This study explores the combination of nivolumab and ipilimumab with sirolimus and prednisone. However, it is important to note that immunotherapy is not effective for everyone, which can leave some patients experiencing side effects while their cancer remains untreated, potentially worsening their condition. Kidney transplant recipients have a higher risk of developing melanoma, primarily because of the immunosuppressive medications they must take to prevent organ rejection. As a result, immunotherapy is a crucial treatment option for these patients, as it helps stimulate their immune systems to identify and attack cancer cells more effectively. The study and trial aim to enhance the success rate of immunotherapy for patients who qualify for its use.

New Study, New Hope

The PD-1 study analyzed clinical trial data from 127 patients with melanoma who received immune checkpoint inhibitors (ICIs) targeting the PD-1 protein. While there were no clear patterns in T-cell levels related to viral stimulation or tumor response, the findings may transform skin cancer treatment by identifying which patients are most likely to benefit from immunotherapies, thereby reducing costs and side effects. PD-1, a receptor typically seen as an inhibitor on exhausted CD8+ T cells, is also vital for the survival of these cells in tissues and for maintaining a stem-like ‘pre-exhausted’ progenitor population. The study found that patients who responded well to treatment had significant macrophage infiltration and heightened activation of immune checkpoint regulators. PD-1 has significant clinical benefits, as it enhances the immune system’s ability to combat cancer by regulating T cells and preventing them from attacking healthy cells. Besides, a combination of PD-1+ Vδ1+ and PD-1+ CD8+ T cells is more likely to display a tissue-resident phenotype compared to their PD-1− counterparts.

Immune checkpoint inhibitors (ICIs) are a form of immunotherapy designed to enhance the immune system’s ability to target and destroy cancer cells by blocking specific proteins. Researchers have developed predictive tests to personalize treatments, which helps save time and resources. Interestingly, some cancers that are not easily detected by αβ T cell surveillance still respond well to checkpoint inhibition.

There has always been a gap between measuring PD-L1 protein levels as a clinical biomarker and the actual activity of the protein within the tumor. Recent findings suggest that Vδ1+ cells could be effective targets for these therapies. This development will enable researchers and clinicians to better identify patients who can benefit from immunotherapy and provide improved treatment options for those who do not respond to existing therapies.

New Trial, New Hope

Immunotherapies are medications that stimulate the immune system to combat cancer. A trial at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins is testing the combination of nivolumab and ipilimumab with sirolimus and prednisone for skin cancers that cannot be surgically removed or have spread in kidney transplant recipients.

Numerous studies have examined the combination of therapies, including immune checkpoint inhibitors, immune checkpoint agonists, and the combination of ipilimumab and nivolumab. So it’s interesting to see how this combination of drugs will help renal patients who develop unresectable or metastatic skin cancer. Nivolumab, a PD-1 inhibitor, and ipilimumab, a CTLA-4 inhibitor, are immunotherapy drugs that help the immune system attack cancer cells in melanoma, metastatic cancer, and renal cell carcinoma. In contrast, sirolimus and prednisone are immunosuppressants that prevent organ rejection in kidney transplant recipients.

The objective of this study is to evaluate the proportion of kidney transplant recipients with advanced cutaneous cancers who, 14 weeks after treatment with prednisone, sirolimus, nivolumab, and ipilimumab, achieve a complete response (CR), partial response (PR), or stable disease (SD) without losing their allograft. I’m interested to see if the study will find any immunological changes in the tumor environment or if they’ll identify any genes that will help with treatment.

For this trial, eligible patients must have confirmed diagnoses of non-uveal melanoma, basal cell carcinoma, Merkel cell carcinoma, or cutaneous squamous cell carcinoma, and should not be suitable for standard non-immunological treatments. Table 1 explains what the participants will receive and gives us an idea of how participants will be assessed. Participants must  have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 (Karnofsky ≥ 60%).  HIV-infected patients on effective antiretroviral therapy with an undetectable viral load are also eligible to join the trial. The criteria for participants are extensive, and some individuals will be excluded. For example, participants who have received a liver, lung, heart, or pancreas transplant; an allogeneic stem cell transplant; or any type of bone marrow transplant will be disqualified. Additionally, patients who are unwilling or unable to undergo dialysis in the event of allograft failure will also be excluded.

Table 1: Summary of how the testing works

Intervention(s)Cycle Duration/TimingNext Steps / Assessments
Sirolimus (PO) and Prednisone (PO) dailyStart 7 days before Cycle 1, Day 1 of immunotherapy—
Nivolumab (IV) over 30 min and Ipilimumab (IV) over 30 min)Day 8 of Cycle 1 and Day 1 of Cycle 2Tumor response assessment 6 weeks after the first nivolumab/ipilimumab dose
Phase in Assessment  in Cycle
Maintenance Nivolumab MonotherapyDay 1 of each cycle (every 4 weeks for up to 24 cycles)Continue if stable disease (SD), partial response (PR), or complete response (CR)Discontinue if disease progression or unacceptable toxicity
Nivolumab + Ipilimumab Combination (for disease progression)Every 3 weeks for 2 cyclesTumor response assessment 6 weeks after combination treatment
Post-Combination Therapy—If SD/PR/CR: Continue nivolumab monotherapyIf progressive disease: options include continuing nivolumab monotherapy or discontinuing study treatment
Imaging and MonitoringThroughout studyMRI during screeningTumor biopsy on studyCT scans and blood sample collection Kidney biopsy if rejection is suspected
Follow-upAfter stopping therapyEvery 12 weeks for 1 yearEvery 16 weeks in year 2Every 20 weeks up to 5 years

Moving Forward with Immunology and Better Cancer Treatments

Immunotherapy trials continue to expand rapidly, with studies designed to deliver highly illustrative data. By looking at the immune response environment in detail, clinicians predict how a patient will respond to different treatments which will help patients in their treatment decision-making process, and create plans that meet patients specific needs while in turn helping to help with their quality of life as they find cancer treatment that fits their personal needs.

Header Image Source: Canva Image by Hailshadow

Edited by: Preeti Prangya Panda

References

  1. Amanda R. Kirane, David Lee, Michael Lowe, M. Usman Ahmad, Saurabh Sharma, Mamatha Serasanambati, Christopher J. Applebee, Elena Safrygina, Allison Betof Warner, Jennifer Wang, Stephanie Le, Banafshé Larijani, Emanual Maverakis. Toward Functional Biomarkers of Response to Neoadjuvant Oncolytic Virus in Stage II Melanoma: Immune-Förster Resonance Energy Transfer and the Dynamic Tumor Immune Microenvironment. JCO Oncology Advances, 2025; (2) DOI: 10.1200/OA-24-00049
  2. Chen, R., Zhu, Y., Shen, Y., Xu, Q., Tang, H., Cui, N., Jiang, L., Dai, X., Chen, W., Lin, Q., & Li, X. (2023). The role of PD-1 signaling in health and immune-related diseases. Frontiers in Immunology, 14, 1163633. https://doi.org/10.3389/fimmu.2023.1163633
  3. Comprehensive Cancer Center LAO, J. S. K., & Lipson, E. J. (2025). Immunotherapy in Combination with Prednisone and Sirolimus for Kidney Transplant Recipients with Unresectable or Metastatic Skin Cancer. National Cancer Institute (NIH). https://www.cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-04306&r=1https://www.cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-04306&r=1 
  4. Davies, D., Kamdar, S., Woolf, R. et al. PD-1 defines a distinct, functional, tissue-adapted state in Vδ1+ T cells with implications for cancer immunotherapy. Nat Cancer 5, 420–432 (2024). https://doi.org/10.1038/s43018-023-00690-0
  5. Gao H, Liu S, Mai Y, et alCombined therapy of prednisone and mTOR inhibitor sirolimus for treating retroperitoneal fibrosisAnnals of the Rheumatic Diseases 2023;82:688-697.
  6. Kooshkaki O, Derakhshani A, Hosseinkhani N, Torabi M, Safaei S, Brunetti O, Racanelli V, Silvestris N, Baradaran B. Combination of Ipilimumab and Nivolumab in Cancers: From Clinical Practice to Ongoing Clinical Trials. Int J Mol Sci. 2020 Jun 22;21(12):4427. doi: 10.3390/ijms21124427. PMID: 32580338; PMCID: PMC7352976.
  7. Rossi, E., Schinzari, G., Maiorano, B. A., Esposito, I., Acampora, A., Romagnoli, J., … Tortora, G. (2021). Immune-Checkpoint Inhibitors in Renal Transplanted Patients Affected by Melanoma: A Systematic Review. Immunotherapy, 14(1), 65–75. https://doi.org/10.2217/imt-2021-0195
  8. Singh, K., Gautam, P.K. Macrophage infiltration in 3D cancer spheroids to recapitulate the TME and unveil interactions within cancer cells and macrophages to modulate chemotherapeutic drug efficacy. BMC Cancer 23, 1201 (2023). https://doi.org/10.1186/s12885-023-11674-9
  9. University of Bath. Researchers shed light on how to predict which skin cancer patients are most likely to respond to immunotherapy. ScienceDaily, (2025); http://www.sciencedaily.com/releases/2025/01/250108143941.htm

Leave a comment

Create a website or blog at WordPress.com

Up ↑