Significance of CD103 <sup>+</sup> tissue-resident memory T cells for predicting the effectiveness of immune checkpoint inhibitors in esophageal cancer

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Immune checkpoint inhibitors (ICIs), including nivolumab, have been approved to treat esophageal cancer. However, these remedies are not fit for all patients with esophageal cancer; therefore, a predictive surrogate marker is needed to assess their effectiveness. CD103 ⁺CD8 ⁺ tumor-infiltrating lymphocytes, defined as tissue-resident memory T cells (T _RM), are promising indicators of response to ICIs, but it remains to be elucidated. This study investigated the association between the efficacy of ICIs and T _RM.

Methods

The relationships between T _RM infiltrating esophageal cancer, clinicopathological features, and prognosis after nivolumab initiation were examined using immunostaining. Tissue samples were obtained from surgically resected specimens of 37 patients with esophageal cancer who received nivolumab as a secondary or subsequent therapy. In addition, T _RM infiltration was compared with programmed death-ligand 1 (PD-L1) expression and blood count parameters as predictors of nivolumab effectiveness.

Results

T _RM-rich patients had a significant survival benefit after nivolumab initiation (12-months overall survival 70.8% vs 37.2%, p = 0.0485; 12-months progression-free survival 31.2% vs 0%, p = 0.0153) and experienced immune-related adverse events more frequently than T _RM-poor patients (6 vs 2 patients). T _RM infiltration was weakly correlated with PD-L1 positivity ( r = 0.374, p = 0.022), but T _RM may indicate more sensitive response to ICIs than PD-L1 expression in this study. Some blood test parameters also weakly correlated with T _RM but did not impact prognosis.

Conclusions

T _RM-rich patients have a favorable prognosis after nivolumab initiation. Our results suggest that T _RM are vital for antitumor immunity and are a promising predictor of ICIs effectiveness.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12885-023-11438-5.

Related collections

Most cited references 40

Record: found
Abstract: found
Article: not found

Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma.

Robert Motzer, Bernard Escudier, David F McDermott … (2016)

Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus in patients with renal-cell carcinoma who had received previous treatment.

0 comments Cited 1207 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

B cells and tertiary lymphoid structures promote immunotherapy response

Beth A Helmink, Sangeetha M Reddy, Jianjun Gao … (2020)

Treatment with immune checkpoint blockade (ICB) has revolutionized cancer therapy. Until now, predictive biomarkers1-10 and strategies to augment clinical response have largely focused on the T cell compartment. However, other immune subsets may also contribute to anti-tumour immunity11-15, although these have been less well-studied in ICB treatment16. A previously conducted neoadjuvant ICB trial in patients with melanoma showed via targeted expression profiling17 that B cell signatures were enriched in the tumours of patients who respond to treatment versus non-responding patients. To build on this, here we performed bulk RNA sequencing and found that B cell markers were the most differentially expressed genes in the tumours of responders versus non-responders. Our findings were corroborated using a computational method (MCP-counter18) to estimate the immune and stromal composition in this and two other ICB-treated cohorts (patients with melanoma and renal cell carcinoma). Histological evaluation highlighted the localization of B cells within tertiary lymphoid structures. We assessed the potential functional contributions of B cells via bulk and single-cell RNA sequencing, which demonstrate clonal expansion and unique functional states of B cells in responders. Mass cytometry showed that switched memory B cells were enriched in the tumours of responders. Together, these data provide insights into the potential role of B cells and tertiary lymphoid structures in the response to ICB treatment, with implications for the development of biomarkers and therapeutic targets.

0 comments Cited 939 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Tertiary lymphoid structures improve immunotherapy and survival in melanoma

Rita Cabrita, Martin Lauss, Adriana Sanna … (2020)

Checkpoint blockade therapies that reactivate tumour-associated T cells can induce durable tumour control and result in the long-term survival of patients with advanced cancers1. Current predictive biomarkers for therapy response include high levels of intratumour immunological activity, a high tumour mutational burden and specific characteristics of the gut microbiota2,3. Although the role of T cells in antitumour responses has thoroughly been studied, other immune cells remain insufficiently explored. Here we use clinical samples of metastatic melanomas to investigate the role of B cells in antitumour responses, and find that the co-occurrence of tumour-associated CD8+ T cells and CD20+ B cells is associated with improved survival, independently of other clinical variables. Immunofluorescence staining of CXCR5 and CXCL13 in combination with CD20 reveals the formation of tertiary lymphoid structures in these CD8+CD20+ tumours. We derived a gene signature associated with tertiary lymphoid structures, which predicted clinical outcomes in cohorts of patients treated with immune checkpoint blockade. Furthermore, B-cell-rich tumours were accompanied by increased levels of TCF7+ naive and/or memory T cells. This was corroborated by digital spatial-profiling data, in which T cells in tumours without tertiary lymphoid structures had a dysfunctional molecular phenotype. Our results indicate that tertiary lymphoid structures have a key role in the immune microenvironment in melanoma, by conferring distinct T cell phenotypes. Therapeutic strategies to induce the formation of tertiary lymphoid structures should be explored to improve responses to cancer immunotherapy.

0 comments Cited 797 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Hiroaki Tanaka: hiroakitan@omu.ac.jp

Journal

Journal ID (nlm-ta): BMC Cancer

Journal ID (iso-abbrev): BMC Cancer

Title: BMC Cancer

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2407

Publication date (Electronic): 20 October 2023

Publication date PMC-release: 20 October 2023

Publication date Collection: 2023

Volume: 23

Electronic Location Identifier: 1011

Affiliations

[1 ]GRID grid.518217.8, ISNI 0000 0005 0893 4200, Department of Gastroenterological Surgery, , Osaka City University Graduate School of Medicine, ; 1-4-3 Asahi-Machi, Abeno-Ku, Osaka, 545-8585 Japan

[2 ]Department of Gastroenterological Surgery, Fuchu Hospital, ( https://ror.org/05q3m8e94) Osaka, Japan

Article

Publisher ID: 11438

DOI: 10.1186/s12885-023-11438-5

PMC ID: 10588150

PubMed ID: 37864146

SO-VID: 2c12cea5-6ce8-4d0a-b94b-f8563826fb1e

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 12 June 2023

Date accepted : 23 September 2023

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: cd103,esophageal cancer,tissue-resident memory t cell,immune checkpoint inhibitor,antitumor immunity,pd-l1

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: cd103, esophageal cancer, tissue-resident memory t cell, immune checkpoint inhibitor, antitumor immunity, pd-l1