October 18th, Shenzhen - BGI-Research, in collaboration with the Sixth Affiliated Hospital of Sun Yat-sen University, published in Cell Reports Medicine a study on the dynamic changes in the tumor microenvironment and drug resistance of rectal cancer (RC) under neoadjuvant chemotherapy (NAC). This study provides important insights into how NAC affects the tumor microenvironment and offers a base for developing effective treatment plans for RC. BGI's single-cell platform, and spatial multi-omics technology, Stereo-seq, played critical roles in this research.

The research paper, titled "Cancer-associated fibroblasts undergoing neoadjuvant chemotherapy suppress rectal cancer revealed by single-cell and spatial transcriptomics", was published in Cell Reports Medicine.

Colorectal cancer (CRC) ranks as the third most common malignancy globally, with RC accounting for approximately 30% of all cases. The incidence of RC is notably higher in China compared to Western countries.

NAC refers to neoadjuvant chemotherapy administered before surgery, which has proven to significantly reduce the local recurrence rate of tumors, preserve organ function, minimize surgical trauma, and avoid the toxic side effects of radiation. With NAC, some patients can even achieve complete clinical remission without surgery.

However, the mechanism by which NAC affects the tumor microenvironment remains unclear, and the association between cellular and molecular composition and therapeutic response requires further study.

Key findings of the study.

The researchers collected paired samples from 29 RC patients before and after treatment and conducted single-cell and spatial transcriptomic sequencing. The study yielded a high-resolution cellular dynamic landscape remodelled by NAC and their associations with therapeutic response. It showed that NAC significantly reshaped the composition of cancer-associated fibroblast (CAF) subsets in the RC microenvironment, which strongly correlates with therapeutic response. The remodelled CAF subsets regulate the tumor microenvironment through spatial recruitment and crosstalk to activate immunity and suppress tumour progression bymultiple cytokines. On the other hand, researchers identified another subtype of CAF cells in the microenvironment that promotes tumor growth and migration, resulting in poorer treatment outcomes.

The combined use of BGI's single-cell platform and Stereo-seq technology is critical in studying the spatial distribution and dynamic changes. "By integrating the data analysis of single-cell and spatial transcriptomics, we were able to systematically study the tumor microenvironment under neoadjuvant chemotherapy," said Pengfei Qin, co-first author of the study and associate researcher from BGI-Research. 

"The application of spatial transcriptomics sequencing has broadened our perspective on studying the spatial distribution, interactions, regulation, and differentiation of cells. This has led to improvements in our methodology and, as a result, more accurate and specific research findings."

The project underwent ethical review and adheres to regulations and privacy protocols.

Read the article: https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(23)00408-1