In Ovarian Cancer, Postchemotherapy Immunological Modification Points to Later Relapse

New research has uncovered immunological changes in some cases of high-grade serous ovarian cancer (HGSOC) following chemotherapy, which the authors say can help clinicians better understand the risk that a particular patient may experience an early recurrence.

The report was published in Frontiers in Immunology.

Most diagnoses of HGSOC are not made until the disease has already advanced, according to this study’s investigators. Chemotherapy is the standard treatment, but the authors say most patients (70%-80%) will experience a recurrence. The result is a 5-year survival rate of just 30% for patients with advanced-stage HGSOC.

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Still, the authors said although some patients will experience recurrence within 6 months of their initial therapy, others do not see recurrence until 5 or 10 years after their initial treatment, highlighting the great need for a better understanding of which factors lead to early or late recurrences so investigators can target such mechanisms and thereby increase survival times. The authors suspected that chemotherapy response might be associated with a specific gene expression signature determined by the tumor microenvironment.

To investigate, they looked at tumor samples from 24 patients with HGSOC who underwent carboplatin and taxol chemotherapy. They compared samples taken prior to therapy to samples taken following therapy to see if gene expression signatures might correlate with recurrence rates and timing.

They found no notable link between gene expression signatures prior to chemotherapy and eventual patient outcomes. However, the samples taken after chemotherapy told a different story.

“[C]hemotherapy induced significant immunological changes in tumors from late recurrence patients, but had no impact on tumors from early recurrence patients,” they said.

In patients who would go on to have late recurrence, chemotherapy induced the downregulation of genes involved in cell proliferation and upregulation of genes involved in apoptosis, they found.

“This was not surprising, since it suggests that chemotherapy effectively induces cancer cell death in patients who would show good response, ie, delayed (instead of early) recurrence,” the authors said.

In patients with late recurrence, the authors found chemotherapy inverted the immune profile in the tumor microenvironment from a pro-tumor phenotype toward an antitumor immune response.

“To the best of our knowledge, this is the first time that a transcriptomic study in HGSOC patients showed that effective carboplatin and taxol chemotherapy induces an antitumor response alongside cancer cell death in good responders but not in poor responders,” they said.

The authors added that HGSOC has generally been seen as an immunologically “cold tumor,” meaning it is unlikely to respond to immunotherapy. However, their data show late-relapse cases have immunological changes after chemotherapy that makes the tumors “hot.”

“Therefore, our finding that carboplatin and taxol chemotherapy converts ovarian tumors from being ‘cold’ towards a ‘hot’ phenotype in patients with late recurrence suggests that these patients are more likely to benefit from immunotherapy,” they said, adding that their findings also suggest that new strategies are needed for patients likely to be poor responders to chemotherapy.

“Ultimately, this underscores the need for practicing personalized medicine to improve survival for ovarian cancer patients,” they concluded.

Reference

Adzibolosu N, Alvero AB, Ali-Fehmi R, et al. Immunological modifications following chemotherapy are associated with delayed recurrence of ovarian cancer. Front Immunol. Published online June 26, 2023. doi:10.3389/fimmu.2023.1204148