RT Journal Article
SR Electronic
T1 Intratumoral microbiota predicts the response to neoadjuvant chemoimmunotherapy in triple-negative breast cancer
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e010365
DO 10.1136/jitc-2024-010365
VO 13
IS 4
A1 Chen, Yilin
A1 Yang, Lu
A1 Huang, Yuhong
A1 Zhu, Teng
A1 Zhang, Liulu
A1 Cheng, Minyi
A1 Wu, Cangui
A1 Li, Peiyong
A1 Liang, Minting
A1 Zhang, Xiaoqi
A1 Peng, Hao
A1 Wang, Kun
YR 2025
UL http://jitc.bmj.com/content/13/4/e010365.abstract
AB Background Neoadjuvant immunotherapy combined with chemotherapy (Chemo-IM) is associated with significantly improved pathological complete response (pCR) rates and long-term survival outcomes in patient with early-stage triple-negative breast cancer (TNBC). However, only a small proportion of patients benefit from the addition of immunotherapy. Here, we explored and confirmed the role of intratumoral microbiota in screening patients with TNBC who are likely to benefit from neoadjuvant Chemo-IM.Methods Patients with previously untreated, non-metastatic TNBC receiving neoadjuvant Chemo-IM were enrolled. Differences in the intratumoral microbiota between the pCR and non-pCR groups were explored via 16S rDNA sequencing (16S-seq). Single-cell transcriptome sequencing (scRNA-seq) was employed to profile the tumor microenvironment (TME). Moreover, correlations between the intratumor microbiota and the TME were explored. Finally, machine-learning models based on the intratumoral microbiota were constructed to predict pCR.Results A total of 89 female patients with early-stage TNBC treated by neoadjuvant Chemo-IM were enrolled. We found that the pCR group had greater diversity and a higher load of intratumoral microbiota than the non-pCR group. Intriguingly, scRNA-seq revealed significantly increased T cell infiltration and decreased tumor-associated macrophage infiltration into tumors in the pCR group. Moreover, intratumoral microbiota load was positively associated with CD4+CXCL13+ T cell infiltration and negatively associated with CD68+SPP1+ macrophage infiltration. Combined analysis of 16S-seq and scRNA-seq data revealed that intratumoral microbiota were present in both cancer and immune cells. Finally, we developed a model incorporating intratumoral microbiota and clinicopathological characteristics, and it showed strong power for predicting pCR to neoadjuvant Chemo-IM.Conclusions Intratumoral microbiota may serve as a strong and specific predictor of the response of patients with early-stage TNBC to neoadjuvant Chemo-IM. Our findings could contribute to the development of individualized Chemo-IM strategies for treating TNBC.Data are available upon reasonable request. Raw data and processed data of single-cell transcriptome sequencing are being submitted to GEO database (accession number is pending). All the other data should be requested to and will be fulfilled by the lead contact.