Imagine a scenario where a rare cancer treatment leads to complete remission. This is precisely what happened in a recent case involving a patient with a particularly aggressive form of cancer called dedifferentiated liposarcoma (DDLPS). This case report sheds light on the potential of immunotherapy in treating this challenging disease.
This patient's story is unique because they had a high tumor mutational burden (TMB) – essentially, their cancer cells had a lot of genetic mutations – and also a high density of tumor-associated macrophages (TAM) in their tumor microenvironment (TME). These factors may have played a crucial role in their positive response to pembrolizumab, an immune checkpoint inhibitor (ICI).
The report, published in the World Journal of Surgical Oncology, focuses on a patient with recurrent retroperitoneal DDLPS. The significance? This is believed to be the first documented instance of a patient with this condition achieving a pathological complete response (pCR) to pembrolizumab (Keytruda).
According to Dr. Shun Abe and his colleagues at Niigata University Graduate School of Medical and Dental Sciences in Japan, retroperitoneal DDLPS tumors are often large when diagnosed, necessitating complete surgical removal as the primary treatment. But here's where it gets controversial: Recurrence rates can be alarmingly high, reaching up to 83.2%, as some studies suggest. This, coupled with limited treatment options for advanced or metastatic soft tissue sarcoma (STS), makes this case all the more compelling.
Recent research indicates that some DDLPS patients may respond to ICI therapy, even though a clear link between TMB and therapeutic response hasn't always been evident. However, the TME – the environment surrounding the tumor – might be the key.
The patient, a 73-year-old man, was already undergoing hormone therapy for prostate cancer when the DDLPS was discovered. After the initial surgical removal of the tumor, the cancer recurred. He underwent multiple rounds of chemotherapy, but the lesions continued to grow. Genomic profiling revealed a high TMB of 13 mutations per megabase, prompting the use of pembrolizumab. The treatment initially led to a partial response, with a 56.7% reduction in target lesions. However, the patient developed an adverse reaction, leading to the discontinuation of pembrolizumab. A second surgery followed, and a histological examination showed a pCR. Fifteen months later, the patient remained disease-free.
This case highlights the potential of ICIs in a specific subset of DDLPS patients and offers valuable insights into potential biomarkers for predicting responses to these therapies. It's worth noting that STS is generally considered "immune cold" with low TMB; in fact, fewer than 1 in 10 patients with STS are believed to have a high TMB.
And this is the part most people miss: The TME wasn't analyzed until after pembrolizumab monotherapy, which could affect the interpretation of the results. It's possible that prior treatment with doxorubicin helped prepare the TME to respond to ICI therapy.
Ultimately, the researchers emphasize that more research is needed to identify which DDLPS patients will benefit from ICIs. They conclude that future studies should focus on refining predictive biomarkers for this malignancy.
What do you think? Does this case change your perspective on immunotherapy for rare cancers? Are you surprised by the high recurrence rate of DDLPS? Share your thoughts in the comments below!
References:
- Abe S, Zhou Q, Ariizumi T, et al. Pathological complete response to pembrolizumab in recurrent retroperitoneal dedifferentiated liposarcoma with high tumor mutational burden: a case report. World J Surg Oncol. 2025;23(1):449. doi:10.1186/s12957-025-04096-3
- Keung EZ, Hornick JL, Bertagnolli MM, Baldini EH, Raut CP. Predictors of outcomes in patients with primary retroperitoneal dedifferentiated liposarcoma undergoing surgery. J Am Coll Surg. 2014;218(2):206-217. doi:10.1016/j.jamcollsurg.2013.10.009
- Zhu MMT, Shenasa E, Nielsen TO. Sarcomas: Immune biomarker expression and checkpoint inhibitor trials. Cancer Treat Rev. 2020;91:102115. doi:10.1016/j.ctrv.2020.102115
- Emens LA, Middleton G. The interplay of immunotherapy and chemotherapy: harnessing potential synergies. Cancer Immunol Res. 2015;3(5):436-443. doi:10.1158/2326-6066.CIR-15-0064
