Progenitor-like exhausted SPRY1+CD8+ T cells potentiate responsiveness to neoadjuvant PD-1 blockade in esophageal squamous cell carcinoma

Liu, Zhichao; Zhang, Yaru; Ma, Ning; Yang, Yang; Ma, Yunlong; Wang, Feng; Wang, Yan; Wei, Jinzhi; Chen, Hongyan; Tartarone, Alfredo; Velotta, Jeffrey B.; Dayyani, Farshid; Gabriel, Emmanuel; Wakefield, Connor J.; Kidane, Biniam; Carbonelli, Cristiano; Long, Lingyun; Liu, Zhihua; Su, Jianzhong; Li, Zhigang

doi:10.1016/j.ccell.2023.09.011

Cited by 21 publications

(9 citation statements)

References 107 publications

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“…Furthermore, the heterogeneity of CD8 + cells of irresponsive to ICB treatment has also been documented. Exhausted CD8 + T cells expressing SPRY1 (CD8 + Tex-SPRY1), by inducing proinflammatory phenotype of macrophages, correlated with complete response to neoadjuvant PD-1 blockade in advanced ESCC [ 24 ]. Our data demonstrated that more CD3 + CD8 + and CD3 + FoxP3 + T cells were distributed in the stroma region of pN1 pretreatment tissues, compared with the pCR ones.…”

Section: Discussionmentioning

confidence: 99%

“…Neoadjuvant chemoradiotherapy induced overexpression of PD-L1 and significant infiltration of T cells and CD86 + macrophages in solid tumors [ 19 – 21 ]. Neoadjuvant immunotherapy in ESCC indicate that high-density infiltration of CD8 + SPRY1 + T cells enhances immunotherapy efficacy [ 24 ]. Studies on neoadjuvant immunotherapy in other solid tumors have found that post-treatment clonal expansion of CD3 + and CD8 + T cells, along with tissue-resident macrophages, were correlated with pathological response [ 17 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

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Immune cell patterns before and after neoadjuvant immune checkpoint blockade combined with chemoradiotherapy in locally advanced esophageal squamous cell carcinoma

Zheng,

Li,

Yuan

et al. 2024

BMC Cancer

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Background Neoadjuvant immune checkpoint blockade (ICB) combined with chemoradiotherapy offers high pathologic complete response (pCR) rate for patients with locally advanced esophageal squamous cell carcinomas (ESCC). But the dynamic tumor immune microenvironment modulated by such neoadjuvant therapy remains unclear. Patients and methods A total of 41 patients with locally advanced ESCC were recruited. All patients received neoadjuvant toripalimab combined with concurrent chemoradiotherapy. Matched pre- and post-treatment tissues were obtained for fluorescent multiplex immunohistochemistry (mIHC) and IHC analyses. The densities and spatial distributions of immune cells were determined by HALO modules. The differences of immune cell patterns before and after neoadjuvant treatment were investigated. Results In the pre-treatment tissues, more stromal CD3 + FoxP3 + Tregs and CD86+/CD163 + macrophages were observed in patients with residual tumor existed in the resected lymph nodes (pN1), compared with patients with pCR. The majority of macrophages were distributed in close proximity to tumor nest in pN1 patients. In the post-treatment tissues, pCR patients had less CD86 + cell infiltration, whereas higher CD86 + cell density was significantly associated with higher tumor regression grades (TRG) in non-pCR patients. When comparing the paired pre- and post-treatment samples, heterogeneous therapy-associated immune cell patterns were found. Upon to the treatment, CD3 + T lymphocytes were slightly increased in pCR patients, but markedly decreased in non-pCR patients. In contrast, a noticeable increase and a less obvious decrease of CD86 + cell infiltration were respectively depicted in non-pCR and pCR patients. Furthermore, opposite trends of the treatment-induced alterations of CD8 + and CD15 + cell infiltrations were observed between pN0 and pN1 patients. Conclusions Collectively, our data demonstrate a comprehensive picture of tumor immune landscape before and after neoadjuvant ICB combined with chemoradiotherapy in ESCC. The infiltration of CD86 + macrophage may serve as an unfavorable indicator for neoadjuvant toripalimab combined with chemoradiotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Immune cell patterns before and after neoadjuvant immune checkpoint blockade combined with chemoradiotherapy in locally advanced esophageal squamous cell carcinoma

Zheng,

Li,

Yuan

et al. 2024

BMC Cancer

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“…The expression level of the E3 ubiquitin ligase MARCH7 in ESCC tissues has been shown to be significantly greater than that in nontumor tissues, and was negatively correlated with tumor-infiltrating immune cells, such as CD8 + T cells[ 40 ]. Moreover, a subpopulation of CD8 + T cells expressing SPRY1 has been found in ESCC tissues after neoadjuvant immune checkpoint blockade, and these cells may possess certain progenitor cell characteristics and exhibit an exhausted phenotype[ 41 ]. Additionally, fibroblast growth factor 2 derived from tumor fibroblasts can induce the expression of SPRY1 in infiltrating T cells and participate in T-cell exhaustion in EC[ 42 ].…”

Section: Dysfunction Of Immune Cellsmentioning

confidence: 99%

Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer

Zhang,

Yu,

Zhao

et al. 2024

World J Gastroenterol

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As a highly invasive malignancy, esophageal cancer (EC) is a global health issue, and was the eighth most prevalent cancer and the sixth leading cause of cancer-related death worldwide in 2020. Due to its highly immunogenic nature, emer-ging immunotherapy approaches, such as immune checkpoint blockade, have demonstrated promising efficacy in treating EC; however, certain limitations and challenges still exist. In addition, tumors may exhibit primary or acquired resistance to immunotherapy in the tumor immune microenvironment (TIME); thus, understanding the TIME is urgent and crucial, especially given the im-portance of an immunosuppressive microenvironment in tumor progression. The aim of this review was to better elucidate the mechanisms of the suppressive TIME, including cell infiltration, immune cell subsets, cytokines and signaling pathways in the tumor microenvironment of EC patients, as well as the downregulated expression of major histocompatibility complex molecules in tumor cells, to obtain a better understanding of the differences in EC patient responses to immunotherapeutic strategies and accurately predict the efficacy of immunotherapies. Therefore, personalized treatments could be developed to maximize the advantages of immunotherapy.

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“…The recent study by Liu et al utilized cutting-edge single-cell RNA sequencing (scRNA-seq) to thoroughly examine the tumor microenvironment (TME) of locally advanced ESCC undergoing NICB therapy ( 6 ). ScRNA-seq is a powerful technique that allows researchers to analyze gene expression at the individual cell level.…”

mentioning

confidence: 99%

“…While the study of Liu et al offers valuable insights, it is essential to acknowledge certain limitations, including the small sample size and disease-specific considerations ( 6 ). A larger cohort is essential for robustness, additional aspects warrant consideration.…”

mentioning

confidence: 99%

Unraveling the intricacies of neoadjuvant immune checkpoint blockade in esophageal squamous cell carcinoma: a comprehensive single-cell perspective

Zou,

Anwar,

Pizzi

et al. 2024

J Thorac Dis

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Progenitor-like exhausted SPRY1+CD8+ T cells potentiate responsiveness to neoadjuvant PD-1 blockade in esophageal squamous cell carcinoma

Cited by 21 publications

References 107 publications

Immune cell patterns before and after neoadjuvant immune checkpoint blockade combined with chemoradiotherapy in locally advanced esophageal squamous cell carcinoma

Immune cell patterns before and after neoadjuvant immune checkpoint blockade combined with chemoradiotherapy in locally advanced esophageal squamous cell carcinoma

Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer

Unraveling the intricacies of neoadjuvant immune checkpoint blockade in esophageal squamous cell carcinoma: a comprehensive single-cell perspective

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