Phenotypic profiling and prognostic significance of immune infiltrates in esophageal squamous cell carcinoma

Pan, Chuqing; Wang, Yu; Liu, Qianwen; Hu, Yihuai; Fu, Jianhua; Xie, Xiuying; Zhang, Shuishen; Xi, Mian; Wen, Jing

doi:10.1080/2162402x.2021.1883890

Cited by 23 publications

(24 citation statements)

References 46 publications

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“…Though many studies of lung cancer have revealed the different effect of cigarette smoker and non-smoker about tumor microenvironment, how cigarette smoke alters ESCC immune infiltrating is largely unknown. In our previous study 18 , heterogeneous immune population infiltrating intraepithelial and stromal region, which was associated with overall survival, was observed. In this study, we further analyzed the effect of cigarette smoking on the immune cell infiltration of ESCC tissue samples.…”

Section: Introductionmentioning

confidence: 77%

Impacts of Cigarette Smoking on the Tumor Immune Microenvironment in Esophageal Squamous Cell Carcinoma

Wang¹,

Pan²,

Cao³

et al. 2022

J. Cancer

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Objective: Cigarette smoking is a carcinogenic factor for esophageal cancer and evidence also indicates its effects on tumor microenvironment in patients with esophageal squamous cell carcinoma (ESCC). Materials and Methods:In our study, we demonstrated nine immune infiltrating cells and markers in non-smokers and smokers of 189 non-drinking ESCC patients with multiplex fluorescent immunohistochemistry (mflHC) staining and multispectral imaging. The impacts of cigarette smoking on tumor microenvironment and patient prognosis were also analyzed. Results: Among 189 ESCC patients of non-drinker, 86 patients was current smokers, while 34 males and 59 females were non-smokers and 10 former-smokers. Among 34 male non-smokers and 83 smokers, distinct immune infiltrating cells, with increased DCs in stromal regions (P=0.033), elevated infiltration of Treg cells in intraepithelial regions (P=0.010) and reduced activate cytotoxic T lymphocytes (aCTLs) in both intraepithelial (P=0.021) and stromal regions (P=0.017), were observed in tumor specimens of smoking males, implying an immune suppressed response during cigarette smoke exposure. For smoking characters, the level of stromal tumor-associated macrophages (TAMs) infiltration was correlated with smoking year after age adjusted (rs=0.352, P=0.002). Though cigarette smoking did not alter the expression of programmed death ligand 1 (PD-L1) in epithelial cells or TAMs in tumor specimens, higher expression of PD-L1 predicted a worse survival in non-smokers but not smokers. Conclusions: Our findings indicated smoking may impair T cell-mediated immune response and supported the possible impacts of cigarette smoking in PD-L1 related research and therapy of ESCC.

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Section: Introductionmentioning

confidence: 77%

Impacts of Cigarette Smoking on the Tumor Immune Microenvironment in Esophageal Squamous Cell Carcinoma

Wang¹,

Pan²,

Cao³

et al. 2022

J. Cancer

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“…Intratumoural CD8+ T cell infiltration was increased in TLS‐mature ESCCs, which is a significant factor correlating with prolonged ESCC survival. 7 Whether TLS B cells or DCs cross‐present tumour antigens to CD8+ T cells or whether CD4+ Th cells are involved in the generation of CD8+ cytotoxic T cell responses inside or outside TLSs have not been settled. 10 As decreased expression of MHC I antigen presentation molecules was observed in mature TLSs compared to immature TLSs, we speculated that increased CD4+ Th cells, which were activated with Th17 signatures in mature TLSs, may take part in priming and enhancing CD8+ T cells outside TLSs in ESCC tissues.…”

Section: Discussionmentioning

confidence: 99%

The prognostic value and molecular properties of tertiary lymphoid structures in oesophageal squamous cell carcinoma

Ling

Zhong

Weng

et al. 2022

Clinical & Translational Med

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Background Tertiary lymphoid structures (TLSs) play key roles in tumour adaptive immunity. However, the prognostic value and molecular properties of TLSs in oesophageal squamous cell carcinoma (ESCC) patients have not been studied. Methods The prognostic values of the presence and maturation status of tumour‐associated TLSs were determined in 394 and 256 ESCC patients from Sun Yat‐sen University Cancer Center (Centre A) and the Cancer Hospital of Shantou University Medical College (Centre B), respectively. A deep‐learning (DL) TLS classifier was established with haematoxylin and eosin (H&E)‐stained slides using an inception‐resnet‐v2 neural network. Digital spatial profiling was performed to determine the cellular and molecular properties of TLSs in ESCC tissues. Results TLSs were observed in 73.1% of ESCCs from Centre A via pathological examination of H&E‐stained primary tumour slides, among which 42.9% were TLS‐mature and 30.2% were TLS‐immature tumours. The established DL TLS classifier yielded favourable sensitivities and specificities for patient TLS identification and maturation evaluation, with which 55.1%, 39.5% and 5.5% of ESCCs from Centre B were identified as TLS‐mature, TLS‐immature and TLS‐negative tumours. Multivariate analyses proved that the presence of mature TLSs was an independent prognostic factor in both the Centre A and Centre B cohorts ( p < .05). Increased proportions of proliferative B, plasma and CD4+ T helper (Th) cells and increased B memory and Th17 signatures were observed in mature TLSs compared to immature ones. Intratumoural CD8+ T infiltration was increased in TLS‐mature ESCC tissues compared to mature TLS‐absent tissues. The combination of mature TLS presence and high CD8+ T infiltration was associated with the best survival in ESCC patients. Conclusions Mature TLSs improve the prognosis of ESCC patients who underwent complete resection. The use of the DL TLS classifier would facilitate precise and efficient evaluation of TLS maturation status and offer a novel probability of ESCC treatment individualization.

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“…Therefore, allergy and cancer have different dendritic cell phenotypes, prevailing the activated DC in atopic subjects, while the antigen presentation by tolerizing DCs is induced in cancer environment preventing anti‐tumour T‐cell responses. The possibility to drive the activation of effector DCs can be a key to stimulate anti‐tumour immunity by the activation of cytotoxic CD8 + lymphocytes against tumour antigens 46 …”

Section: Role Of Immune Cells In Allergy and Cancermentioning

confidence: 99%

“…The possibility to drive the activation of effector DCs can be a key to stimulate anti‐tumour immunity by the activation of cytotoxic CD8 + lymphocytes against tumour antigens. 46 …”

Section: Role Of Immune Cells In Allergy and Cancermentioning

confidence: 99%

AllergoOncology: Role of immune cells and immune proteins

Gioacchino

Valle

Allegra

et al. 2022

Clinical & Translational All

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Background: Immune cells and immune proteins play a pivotal role in host responses to pathogens, allergens and cancer. Understanding the crosstalk between allergic response and cancer, immune surveillance, immunomodulation, role of immunoglobulin E (IgE)-mediated functions and help to develop novel therapeutic strategies. Allergy and oncology show two opposite scenarios: whereas immune tolerance is desired in allergy, it is detrimental in cancer.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Phenotypic profiling and prognostic significance of immune infiltrates in esophageal squamous cell carcinoma

Cited by 23 publications

References 46 publications

Impacts of Cigarette Smoking on the Tumor Immune Microenvironment in Esophageal Squamous Cell Carcinoma

Impacts of Cigarette Smoking on the Tumor Immune Microenvironment in Esophageal Squamous Cell Carcinoma

The prognostic value and molecular properties of tertiary lymphoid structures in oesophageal squamous cell carcinoma

AllergoOncology: Role of immune cells and immune proteins

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