Histologic evaluation of host immune microenvironment and its prognostic significance in oral tongue squamous cell carcinoma: a comparative study on lymphocytic host response (LHR) and tumor infiltrating lymphocytes (TILs)

Xu, Bin; Salama, Abeer M.; Valero, Cristina; Yuan, Amy; Khimraj, Anjanie; Saliba, Maelle; Zanoni, Daniella Karassawa; Ganly, Ian; Ghossein, Ronald; Patel, Snehal G.; Katabi, Nora

doi:10.1016/j.prp.2021.153473

Cited by 4 publications

(4 citation statements)

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“…Our data have also shown negative correlations between the expressions of CD73 and ITGA6 genes and the proportions of CD8+ T cells and B cells in the tumor (Table S4). Other immune cells with anti‐tumor effects, including NK cells and M1 macrophages, were also associated with better prognosis of OSCC patients 55–58 . The GPC tumors had more activated CD4+ T cells, activated NK cells, M0 and M1 macrophages, compared to negative margins (Table S4).…”

Section: Discussionmentioning

confidence: 92%

“…Other immune cells with anti‐tumor effects, including NK cells and M1 macrophages, were also associated with better prognosis of OSCC patients. 55 , 56 , 57 , 58 The GPC tumors had more activated CD4+ T cells, activated NK cells, M0 and M1 macrophages, compared to negative margins (Table S4 ). Contrarily, both CD4+ T cells and M0 macrophages were fewer in the BPC tumors compared to the negative margins.…”

Section: Discussionmentioning

confidence: 99%

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Overexpression of CD73 is associated with recurrence and poor prognosis of gingivobuccal oral cancer as revealed by transcriptome and deep immune profiling of paired tumor and margin tissues

et al. 2023

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BackgroundFor various cancers, differences in response to treatment and subsequent survival period have been reported to be associated with variation in immune contextures.AimWe sought to identify whether such association exists in respect of gingivobuccal oral cancer.Materials and methodsWe performed deep immune profiling of tumor and margin tissues collected from 46 treatment naïve, Human Papillomavirus (HPV) negative, patients. Each patient was followed for 24 months and prognosis (recurrence/death) noted. Key findings were validated by comparing with TCGA‐HNSC cohort data.ResultsAbout 28% of patients showed poor post‐treatment prognosis. These patients exhibited a high probability of recurrence even within 1 year and death within 2 years. There was restricted immune cell infiltration in tumor, but not in margin, among these patients. Reduced expression of eight immune‐related genes (IRGs) (NT5E, THRA, RBP1, TLR4, ITGA6, BMPR1B, ITGAV, SSTR1) in tumor strongly predicted better quality of prognosis, both in our patient cohort and in TCGA‐HNSC cohort. Tumors of patients with better prognosis were associated with (a) lower CD73+ cells with concomitant lower expression level of NT5E/CD73, (b) higher proportions of CD4+ and CD8+ T cells, B cells, NK cells, M1 macrophages, (c) higher %Granzyme+ cells, (d) higher TCR and BCR repertoire diversities. CD73 expression in tumor was associated with low CD8+ and CD4+ T cells, low immune repertoire diversity, and advanced cancer stage.Discussion and conclusionHigh infiltration of anti‐tumor immune cells in both tumors and margins results in good prognosis, while in patients with minimal infiltration in tumors in spite of high infiltration in margins results in poor prognosis. Targeted CD73 immune‐checkpoint inhibition may improve clinical outcome.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Overexpression of CD73 is associated with recurrence and poor prognosis of gingivobuccal oral cancer as revealed by transcriptome and deep immune profiling of paired tumor and margin tissues

et al. 2023

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“…Although the inflammatory response is considered as an attempt of an organism to eradicate tumor cells, and evasion of the immune destruction is considered one of the hallmarks of cancer, the prognostic role of the intensity of the inflammatory response, in the dependency of complex cell populations, in OSCC has generated inconsistent results. However, after the 2017 standardized protocol for assessing infiltrating lymphocytes in solid tumors based on hematoxylin and eosin‐stained slides, 12 a consistent association of TILs with poor outcomes has been verified in many studies 13,25,26 . Furthermore, studies characterizing TILs in OSCCs showed the existent of an immunosuppressive milieu containing regulatory T cells, an immunosuppressive subset of CD4 + T cells 27 .…”

Section: Discussionmentioning

confidence: 96%

“…However, after the 2017 standardized protocol for assessing infiltrating lymphocytes in solid tumors based on hematoxylin and eosin-stained slides, 12 a consistent association of TILs with poor outcomes has been verified in many studies. 13,25,26 Furthermore, studies characterizing TILs in OSCCs showed the existent of an immunosuppressive milieu containing regulatory T cells, an immunosuppressive subset of CD4 + T cells. 27 In this study, TILs set at a 20% cut-off (also when set at 30%, data not shown) were associated with poor CSS, but not as an independent factor.…”

Section: Discussionmentioning

confidence: 99%

Exploring the combination of tumor‐stroma ratio, tumor‐infiltrating lymphocytes, and tumor budding with WHO histopathological grading on early‐stage oral squamous cell carcinoma prognosis

Silva

Dólens

Paranaíba

et al. 2022

J Oral Pathology Medicine

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Background While the relevance of the World Health Organization histopathological grading system as a prognostic tool for oral squamous cell carcinoma has received many critics, other histopathological features such as tumor‐stroma ratio, tumor‐infiltrating lymphocytes, and tumor budding are displaying promising results. Here, we evaluated the prognostic impact of the incorporation of tumor‐stroma ratio, tumor‐infiltrating lymphocytes, and tumor budding into World Health Organization histopathological grading for patients with oral squamous cell carcinoma. Methods A total of 95 patients with early‐stage oral squamous cell carcinoma were enrolled in the study, and World Health Organization tumor grading, tumor‐stroma ratio, tumor‐infiltrating lymphocytes, and tumor budding were evaluated in surgical slides stained with hematoxylin and eosin. Survival analyses for cancer‐specific survival and disease‐free survival were performed using Cox regression models, and receiver operating characteristic curves were applied for assessment of the performance of the combinations. Results Tumor‐stroma ratio (stroma‐rich) was significantly and independently associated with both shortened cancer‐specific survival and poor disease‐free survival, individually and in combination with World Health Organization histopathological grading. The combination of tumor‐stroma ratio with World Health Organization grading did not improve the discriminatory ability compared to tumor‐stroma ratio alone. Although low tumor‐infiltrating lymphocytes were associated with shortened cancer‐specific survival, the association did not withstand multivariate analysis. However, in combination with World Health Organization grading, low tumor‐infiltrating lymphocytes were independently associated with poor cancer‐specific survival. The combination of tumor‐infiltrating lymphocytes and World Health Organization histopathological grading displayed a better discrimination of poor cancer‐specific survival than tumor‐infiltrating lymphocytes alone, but not at a significant level. Conclusion Our findings support tumor‐stroma ratio as a potential prognostic marker for patients with oral squamous cell carcinoma, and the incorporation of tumor‐infiltrating lymphocytes into the World Health Organization grading system improves the prognostic ability of the tumor grading alone.

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Tumour-infiltrating lymphocytes in oropharyngeal cancer: a validation study according to the criteria of the International Immuno-Oncology Biomarker Working Group

et al. 2022

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Background The evaluation of immune response can aid in prediction of cancer behaviour. Here, we assessed the prognostic significance of tumour-infiltrating lymphocytes (TILs) in oropharyngeal squamous cell carcinoma (OPSCC). Methods A total of 182 patients treated for OPSCC were included in this study. Assessment of TILs was conducted on tumour sections stained with standard haematoxylin and eosin (HE) staining. We used the scoring criteria proposed by the International Immuno-Oncology Biomarker Working Group. Results The multivariable analysis showed that TILs associated with disease-specific survival with a hazard ratio (HR) of 2.13 (95% CI 1.14–3.96; P = 0.017). Similarly, TILs associated significantly with overall survival with HR of 1.87 (95% CI 1.11–3.13; P = 0.018). In a sub-analysis of HPV-positive and HPV-negative cases separately, TILs showed a significant prognostic value in both groups (P < 0.05). Conclusion The evaluation of TILs as proposed by the International Immuno-Oncology Biomarker Working Group is a simple and promising method in prediction of survival of OPSCC. It is easily applicable and after further validation can be implemented in the routine pathological report as a basic immune parameter.

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Histologic evaluation of host immune microenvironment and its prognostic significance in oral tongue squamous cell carcinoma: a comparative study on lymphocytic host response (LHR) and tumor infiltrating lymphocytes (TILs)

Cited by 4 publications

References 26 publications

Overexpression of CD73 is associated with recurrence and poor prognosis of gingivobuccal oral cancer as revealed by transcriptome and deep immune profiling of paired tumor and margin tissues

Overexpression of CD73 is associated with recurrence and poor prognosis of gingivobuccal oral cancer as revealed by transcriptome and deep immune profiling of paired tumor and margin tissues

Exploring the combination of tumor‐stroma ratio, tumor‐infiltrating lymphocytes, and tumor budding with WHO histopathological grading on early‐stage oral squamous cell carcinoma prognosis

Tumour-infiltrating lymphocytes in oropharyngeal cancer: a validation study according to the criteria of the International Immuno-Oncology Biomarker Working Group

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