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Gastric Cancer Chemotherapy Response, Prognoses Predicted With Blood-Based Immune Proteomics

NEW YORK – New research suggests that immune proteomic profiles present in blood serum samples taken prior to treatment can provide prognostic clues in gastric cancer patients receiving chemotherapy ahead of surgery.

"Preoperative chemotherapy induces a sophisticated systemic immune response indicated by dynamic serum proteomics," co-senior authors Xuefei Wang, Yihong Sun, and Yuehong Cui, all from Fudan University, and their colleagues reported. They further noted that they came up with a serum protein score for predicting neoadjuvant chemotherapy response.

In their paper published in Cell Reports Medicine on Tuesday, the researchers turned to antibody assay-based proteomics to profile blood serum samples from 90 individuals with gastric adenocarcinoma. These included 37 pretreatment samples, eight samples collected from patients during treatment, and 83 posttreatment samples, they explained, with profiling done at Sinotech Genomics in China using a proximity extension assay centered on an Olink proteomics target 96 inflammation panel.

From there, the team compared systemic immune patterns drawn from the blood serum samples to immune features in the tumor microenvironment, which were assessed using a combination of pathology testing on 90 matched tumor samples, immunohistochemistry on 70 tumor samples, multiplex immunotherapy testing on 52 of the tumor samples, and RNA sequencing, which was applied to 22 of the tumor samples.

In their search for factors that tracked with outcome measurements such as tumor regression, progression-free survival, and overall survival, the investigators highlighted neoadjuvant chemotherapy response ties to both systematic immune features found in the blood and more local immune microenvironment features, including PD-L1 levels.

In particular, the team explained, neoadjuvant chemotherapy responses appeared to coincide with PD-L1 levels in posttreatment tumor stromal samples as well as blood samples collected prior to treatment, which may be amenable to clinical testing for prognostic purposes. On the survival side, the analyses flagged proteins in posttreatment blood serum samples that seemed to track with poorer progression-free and overall survival, including levels of the interleukin 10 receptor subunit beta (IL10RB).

Those results, in turn, prompted the researchers to establish a pretreatment serum response predictive score (PSRscore) based on blood serum levels of the CCL3, IL15RA, CXCL5, and CCL20 proteins. They estimated that more than three-quarters of individuals with high PSRscores are among neoadjuvant chemotherapy responders, while the majority of those with low PSRscores are expected to fall into a non-responder category.

"This work emphasized the fundamental, but largely underestimated, role of systemic immunity in the preoperative chemotherapy of gastric cancer," the authors wrote, "supporting a patient stratification strategy based on pretreatment serum immune proteomics and highlighting the importance of profiling immunity as a whole in future studies."

Even so, they cautioned that "establishment of the PSRscore was based on an Asian cohort receiving platinum-based chemotherapies," suggesting that immune marker performance in non-Asian gastric cancer patients on taxol-based treatment strategies "needs to be further validated."