Tumor microenvironment remodeling after neoadjuvant immunotherapy in non-small cell lung cancer revealed by single-cell RNA sequencing

Genome Medicine, 2023 · DOI: https://doi.org/10.1186/s13073-023-01164-9 · Published: February 15, 2023

Simple Explanation

This study explores how the environment around lung cancer cells changes after treatment with immunotherapy and chemotherapy before surgery. Researchers analyzed individual cells from patient tumor samples to understand which cells are present and how they are behaving during treatment. The study identifies specific changes in the tumor environment that are linked to whether the treatment is effective, offering potential targets for improving immunotherapy.

Study Duration

September 2019 to May 2021

Participants

39 patients with resectable NSCLC

Evidence Level

Not specified

Key Findings

1
Cancer cells from patients who responded well to treatment showed signs of presenting antigens, which helps the immune system recognize and attack them.
2
Specific types of B cells and monocytes were more abundant in patients who responded well, and these could be used to predict who will benefit from immunotherapy.
3
Cancer cells from patients who did not respond well showed increased estrogen metabolism and elevated levels of estrogen, which may suppress the immune system.

Research Summary

This study investigated the tumor microenvironment (TME) remodeling in non-small cell lung cancer (NSCLC) patients after neoadjuvant PD-1 blockade combined with chemotherapy using single-cell RNA sequencing. The study identified distinct therapy-induced cancer cell transcriptomes associated with clinical response, including the upregulation of MHC-II antigen presentation in major pathologic response (MPR) patients and overexpression of estrogen metabolism enzymes in non-MPR (NMPR) patients. The study also revealed the dynamics of immune cell lineages, such as the expansion and activation of cytotoxic T cells and CD16+ NK cells, the reduction of immunosuppressive Tregs, and the remodeling of tumor-associated macrophages (TAMs) into a neutral phenotype after therapy.

Practical Implications

Predicting Treatment Response

FCRL4+ FCRL5+ memory B cells and CD16+CX3CR1+ monocytes can be used as biomarkers to predict which patients will respond well to immunotherapy.

Overcoming Immunotherapy Resistance

Targeting estrogen metabolism in cancer cells may improve the effectiveness of immunotherapy for patients who do not respond well to current treatments.

Combination Therapies

Combining anti-estrogen therapies with ICB may be a potential strategy to enhance the response to immunotherapy.

Study Limitations

1
Small patient sample size
2
Patients received combination immunotherapy and chemotherapy, making it difficult to isolate the effects of each treatment
3
Independent validations of the hypothesis regarding CCL3+ neutrophils and SPP1+ TAMs were not available

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