Are Calreticulin Levels Related to Ovarian Cancer Prognosis?
Posted: Monday, December 16, 2019
Exposure of the calcium-binding protein calreticulin on the membrane of malignant cells occurs when cells are experiencing endoplasmic reticulum distress, and the level of calreticulin expressed in high-grade serous ovarian carcinomas appears to have prognostic value. Clinically relevant innate and adaptive immune responses are active with high calreticulin levels, according to data published by Jitka Fucikova, PhD, of Charles University in Prague, Czech Republic, and colleagues in the Journal for ImmunoTherapy of Cancer.
The researchers used three cohorts of patients with both primary and metastatic high-grade serous ovarian cancers; one retrospective group had not received neoadjuvant chemotherapy, one retrospective group had received neoadjuvant chemotherapy, and the last was a prospective collection of patients who received neoadjuvant chemotherapy. Tumor samples were obtained from patients in each group and were analyzed using immunohistochemistry, flow cytometry, and degranulation studies.
Their data showed that calreticulin exposure on the surface of both primary and metastatic high-grade serous carcinomas is driven by an endoplasmic reticulum–mediated stress response. This response was found to be independent of chemotherapy. Furthermore, calreticulin expression was found to be associated with a favorable disease outcome upon tumor resection and suggests a Th1-polarized cytotoxic CD8 T-cell response, supporting anticancer immunity.
“It can be speculated that [patients with low levels of calreticulin] would benefit from neoadjuvant or adjuvant chemotherapeutic regimens that are known to drive robust endoplasmic reticulum stress responses in the context of immunogenic cell death, such as oxaliplatin, doxorubicin, and other anthracyclines,” concluded the authors.
Disclosure: For full disclosures of the study authors, visit jitc.biomedcentral.com.