Imagine a future where a simple combination therapy could dramatically extend the lives of patients battling an aggressive form of lung cancer. This isn’t science fiction—it’s the promise of a groundbreaking treatment. A recent study has revealed that pairing atezolizumab (Tecentriq) with dendritic cell (DC) vaccination may offer long-term survival benefits for patients with extensive-stage small cell lung cancer (ES-SCLC), a disease notorious for its poor prognosis. But here’s where it gets even more intriguing: the key to this success might lie in a specific type of immune cell, the XCR1-positive conventional type 1 dendritic cell, which appears to mediate the response to atezolizumab.
In a phase 1b/2 trial (NCT04487756) presented at the Society for Immunotherapy of Cancer 2025 Annual Meeting, researchers found that this combination therapy produced remarkable outcomes in a small group of patients. After a median follow-up of 25.7 months, 18 patients who received a median of 3 doses of DC vaccination (range, 1-6) showed a median progression-free survival (PFS) of 4.7 months and a median overall survival (OS) of 11.2 months. Even more striking, 33% of patients survived beyond 24 months, with 22% achieving progression-free status at this milestone.
And this is the part most people miss: the study also uncovered a fascinating link between immune cell changes and survival. Patients with an expansion of XCR1-positive conventional type 1 dendritic cells (cDC1s) and CXCR5-positive, PD-1–positive, CD8-positive T cells experienced significantly longer survival. For instance, those with a higher change in CXCR5-positive T cells (0.42 or higher) had a median OS of 26.0 months, compared to just 6.7 months in patients with lower changes. Similarly, patients with an expansion of XCR1-positive DCs within cDC1s saw a median OS of 19.0 months, versus 6.3 months in those without this expansion.
But here’s where it gets controversial: while the therapy showed a favorable safety profile, the question remains—can these findings be replicated in larger, more diverse patient populations? And what role does tumor mutational burden (TMB) or molecular subtype truly play in these outcomes? The investigators found no significant differences in long-term survival based on these factors, but does this mean they’re irrelevant, or are we missing something?
Maria Gonzalez-Cao, MD, from Dexeus University Hospital in Barcelona, Spain, and her coauthors emphasized the potential of cDC1s as mediators of response to atezolizumab. However, the study’s small cohort size and specific patient demographics leave room for debate. For example, long survivors were more likely to have brain metastases, while those without long survival had a higher incidence of bone metastases. Does this suggest certain metastasis types respond better to the therapy, or is it merely a coincidence?
The trial’s design is equally compelling. Patients received standard induction chemotherapy plus atezolizumab, followed by up to 6 doses of mature DCs and continued atezolizumab treatment. Investigators used flow cytometry to assess DC populations and exhausted CD8-positive T cell subsets, defining long survival as beyond 18 months. Primary endpoints included PFS at 6 months and adverse event monitoring, while secondary endpoints focused on clinical benefit duration, OS, and objective response rate.
Eligibility criteria were stringent, including histologically confirmed ES-SCLC, no prior advanced cancer treatment, and an ECOG performance status of 0 or 1. Of the 20 patients enrolled, 6 were categorized as “long survivors,” with a median age of 60 years, compared to 62 years in the non-long survivor group. Interestingly, long survivors were more likely to be female and had a higher median TMB (29 vs. 23).
As we ponder these findings, one question lingers: Could this combination therapy revolutionize ES-SCLC treatment, or is it just a promising but niche solution? What do you think? Share your thoughts in the comments—let’s spark a conversation about the future of cancer immunotherapy.