Stromal cells offer chemotherapy clue in early lung cancer

Podoplanin-positive cancer-associated fibroblasts (CAFs) predict recurrence in stage I lung adenocarcinoma, which could help identify patients suited for adjuvant chemotherapy, research shows.

When patients were followed up for 5 years after surgery, the proportion without recurrence was 71.5% in patients with podoplanin-positive CAFs and 94.4% in those without.

The presence of podoplanin-positive CAFs was a strong, independent predictor for recurrence, increasing the risk by a factor of 3.5 compared with their absence.

"The present study is the first to show that a certain type of tumor stromal cell is a recurrence predictor, independent of other established prognostic factors in patients with lung cancer," say Genichiro Ishii (National Cancer Center Hospital East, Kashiwa, Japan) and colleagues.

Recent research from animal and in vitro studies has begun to reveal the influential role of the tumor microenvironment on tumor progression.

The authors examined levels of CD204-positivity in tumor-associated macrophages (TAMs) and podoplanin-positivity in CAFs ‑ both of which have been associated with enhanced tumor proliferation.

The study, reported in Chest, included 304 patients with stage I lung adenocarcinoma who underwent surgical resection for their tumors. Researchers followed up patients at 3‑6 month intervals for a median of 87 months.

The 5-year recurrence-free rate was significantly greater in patients with low CD204-positivity than those with high CD204-positivity (93.4 vs 79.8%), and high CD204-positivity was identified as a significant risk factor for recurrence.

However, podoplanin-positive CAFs were found to be an independent predictor for recurrence, independent of, and more powerful than the established prognostic factors visceral pleural invasion (hazard ratio [HR]=3.4) and intratumoral vascular invasion (HR=3.1).

The authors believe that, while the use of adjuvant chemotherapy in stage I patients is controversial, their results could help identify patients who are likely to benefit most.

CAFs are associated with resistance to chemotherapy and antineovascular endothelial growth factor therapy, and podoplanin has been shown to be responsible for enhancing tumor formation. Therefore, the authors suggest podoplanin could become a therapeutic target itself in future research.

Ishii et al say that further research is needed to confirm their findings and establish the efficacy of adjuvant chemotherapy in high-risk patients: "Clarification of the role of stromal cells as a prognostic factor may lead to a novel risk classification of patients with lung adenocarcinoma, and more effective treatment strategies."

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