Integration of expression rate and absolute cell counts of PD-1+ stromal tumour-infiltrating lymphocytes: Prognostic significance in esophageal squamous cell carcinoma

Abstract Background: Cancer cells induce the infiltration of various immune cells that are located or distributed in different sites and play multiple roles, which have recently been proposed to predict clinical outcomes. We therefore studied the prognostic significance of the presence of tumour-infiltrating lymphocytes (TILs) and the ratios between different types of immune cells in hypopharyngeal squamous cell carcinoma (HPSCC). Methods: We retrospectively analysed 132 consecutive patients diagnosed with advanced HPSCC in 2013-2017. Tumoural parenchyma was immunohistochemically counted manually for the number of CD8, CD4 and Foxp3 cells. The ratios of CD8/Foxp3 and CD8/CD4 ratios were calculated for each specimen and analyzed with respect to patient clinicopathological variables and prognosis. Results: HPSCC patients with high levels of TILs showed evident correlations with well differentiated tumors (P < 0.05). Moreover, Foxp3+ TIL is also associated with overall staging group and T category (P =0.048 and P= 0.046, respectively). Kaplan-Meier analysis showed that high CD8 and FoxP3 infiltration correlated with favourable overall survival (OS, P = 0.019 and P = 0.001), disease-free survival (DFS, P = 0.045 and P = 0.028) and distant metastasis-free survival (DMFS, P = 0.034 and P = 0.009), respectively, but only Foxp3 displayed prognostic significance for DMFS in multivariate analysis (MVA). In the lymphocyte ratio analysis, CD8/Foxp3 appeared to play a pivotal role, and patients with a high CD8/Foxp3 ratio had a superior 3-year DFS and DMFS compared with those a low CD8/Foxp3 ratio in both univariate analysis (UVA) and MVA (P = 0.015 and P=0.011). A high CD8/CD4 ratio was associated with better DFS and local relapse-free survival (LRFS) in UVA, and was an independent prognostic factor for improved LRFS in MVA (P = 0.040).Conclusion: Although high TILs levels were determined to be prognostically significant in advanced HPSCC, the ratios of these subsets may be more informative. Particularly, a higher ratio of CD8/Foxp3 accurately predicts prognosis for improved DFS and DMFS, and an increased CD8/CD4 ratio is an independent predictor for favourable LRFS.

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506 TO STUDY THE CLINICAL IMPACT AND PROGNOSTIC VALUE OF TUMOR INFILTRATING LYMPHOCYTES IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Diseases of the Esophagus ◽

10.1093/dote/doaa087.132 ◽

2020 ◽

Vol 33 (Supplement_1) ◽

Author(s):

N Uma Baskaran ◽

A M ◽

S Rajendiran

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Tumor Infiltrating Lymphocytes ◽

Good Prognosis ◽

Tumour Tissue ◽

Stromal Compartment ◽

Tumour Infiltrating Lymphocytes ◽

Infiltrating Lymphocytes

Abstract Esophageal cancer is the sixth most common cause of death due to cancer worldwide, of which Esophageal Squamous cell carcinoma (ESCC) is the most prevalent type. The presence of Tumour Infiltrating Lymphocytes (TILs) in a tumour indicates a good prognosis of the cancer following immunotherapy. Numeral immunological inhibitors have been developed to treat a variety of cancers, however the role of TILs in ESCC has not been substantiated with proper evidence. Methods The study enrolled 27 patients of ESCC between the years 2014–2019.The evaluation was based on the criteria laid down by the International TILs Working Group 2014 (recorded in percentage based on the area of stromal compartment invaded by the mononuclear inflammatory cells). Scoring was done in 400x field as follows: Score 0- No infiltrating lymphocytes. Score 1- Mild increase in infiltrating lymphocytes in the tumour nest or stroma. Score 2- Increase in infiltrating lymphocytes interwoven with the tumour tissue. Score 3- Prominent infiltrating lymphocytes incorporated in the tumour tissue. Results A total of 27 cases were studied, of which 17 were males (63%) and 10 were females (37%). The commonest age group was 60–70 years (12 cases- 44.4%). 22 cases had tumours sized between 3-7 cm (81.4%). pT1–1 case (0.03%). pT2–10 cases (37.03%). pT3–16 cases (59.25%). TILs were further scored based on the standard scoring system, and the results were as follows: Score 0 in 3 cases (11.11%). Score 1 in 14 cases (51.8%). Score 2 in 4 cases (14.8%). Score 3 in 6 cases (22.22%). Conclusion In conclusion, the commonest score of 1 was seen in 51.8% of the cases and that of score 3 was seen in 22.22% of the cases. Tumour Infiltrating Lymphocytes can hence serve as a predictor for good prognosis of Esophageal Squamous Cell Carcinoma following surgery or radiotherapy/chemotherapy.

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The prognostic significance of tumour infiltrating lymphocytes in oral squamous cell carcinoma

Polish Journal of Pathology ◽

10.5114/pjp.2019.93130 ◽

2019 ◽

Vol 70 (4) ◽

pp. 277-285

Author(s):

Mariusz Książek ◽

Bogumił Lewandowski ◽

Robert Brodowski ◽

Paweł Pakla ◽

Marta Kawalec-Książek ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Prognostic Significance ◽

Tumour Infiltrating Lymphocytes ◽

Infiltrating Lymphocytes

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CLINICAL IMPACT AND PROGNOSTIC VALUE OF TUMOR INFILTRATING LYMPHOCYTES IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

10.36106/gjra/8901058 ◽

2020 ◽

pp. 1-4

Author(s):

Nikitha Uma Baskaran ◽

Arthi M ◽

Swaminathan Rajendiran

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Tumor Infiltrating Lymphocytes ◽

Good Prognosis ◽

Age Group ◽

Tumour Infiltrating Lymphocytes ◽

Infiltrating Lymphocytes

Background: Esophageal Squamous cell carcinoma is the most prevalent type of Esophageal cancer in the world. The presence of Tumour infiltrating lymphocytes indicates a good prognosis of the cancer and this may suggest a good response to immunotherapy. Numerous immunological inhibitors have been developed to treat a variety of cancers; however, the role of Tumour Infiltrating Lymphocytes in Esophageal Squamous Cell Carcinoma has not been substantiated with proper evidence. Methodology: The study enrolled 27 patients of Esophageal Squamous Cell Carcinoma between the years 2014-2019. The evaluation was based on the criteria laid down by the International Tumour Infiltrating Lymphocytes Working Group 2014 and scoring of the same was done in 400x field and were reported. Results: A total of 27 cases were studied, of which 17 were males and 10 were females. The commonest age group was 60-70 years. 22 cases had tumours sized between 3-7cm. Tumour grading of pT1 was seen in 1 case, grading of pT2 in 10 cases and pT3 in 16 cases. Tumour Infiltrating Lymphocytes were scored based on the standard scoring system, and the results showed that 3 cases were of Score 0, 14 cases of Score 1, 4 cases of Score 2, and 6 cases of Score 3. Conclusion: The commonest score of 1 was seen in 51.8% of the cases and that of score 3 was seen in 22.22% of the cases. Tumour Infiltrating Lymphocytes can hence serve as a predictor for good prognosis of Esophageal Squamous Cell Carcinoma following surgery or radiotherapy/chemotherapy.

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Faculty Opinions recommendation of Clinicopathological and prognostic significance of survivin over-expression in patients with esophageal squamous cell carcinoma: a meta-analysis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717961987.793468751 ◽

2013 ◽

Author(s):

David Katzka

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Meta Analysis ◽

Prognostic Significance ◽

Over Expression

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CALM1 promotes progression and dampens chemosensitivity to EGFR inhibitor in esophageal squamous cell carcinoma

Cancer Cell International ◽

10.1186/s12935-021-01801-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Tao Liu ◽

Xiujuan Han ◽

Shutao Zheng ◽

Qing Liu ◽

Aerziguli Tuerxun ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Prognostic Significance ◽

Xenograft Model ◽

Combined Effect ◽

Egfr Inhibitor ◽

Knock Out ◽

And Migration

Abstract Background Calmodulin1 (CALM1) has been identified as one of the overexpression genes in a variety of cancers and EGFR inhibitor have been widely used in clinical treatment but it is unknown whether CALM1 and epidermal growth factor receptor (EGFR) have a synergistic effect in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to explore the synergistic effects of knock-out CALM1 combined with EGFR inhibitor (Afatinib) and to elucidate the role of CALM1 in sensitizing the resistance to Afatinib in ESCC. Method Immunohistochemistry (IHC) and qRT-PCR were used to examine the expression of CALM1 and EGFR in ESCC tissues. Kaplan–Meier survival analysis was used to analyze the clinical and prognostic significance of CALM1 and EGFR expression in ESCC. Furthermore, to evaluate the biological function of CALM1 in ESCC, the latest gene editing technique CRISPR/Cas9(Clustered regularly interspaced short palindromic repeats)was applied to knockout CALM1 in ESCC cell lines KYSE150, Eca109 and TE-1. MTT, flow cytometry, Transwell migration, scratch wound-healing and colony formation assays were performed to assay the combined effect of knock-out CALM1 and EGFR inhibitor on ESCC cell proliferation and migration. In addition, nude mice xenograft model was used to observe the synergistic inhibition of knock-out CALM1 and Afatinib. Results Both CALM1 and EGFR were found to be significantly over-expressed in ESCC compared with paired normal control. Over-expressed CALM1 and EGFR were significantly associated with clinical stage, T classification and poor overall prognosis, respectively. In vitro, the combined effect of knock-out CALM1 mediated by the lentivirus and EGFR inhibitor was shown to be capable of inhibiting the proliferation, inducing cell cycle arrest at G1/S stage and increasing apoptosis of KYSE-150 and Eca109 cells; invasion and migration were also suppressed. In vivo, the results of tumor weight and total fluorescence were markedly reduced compared with the sgCtrl-infected group and sgCAML1 group. Conclusion Our data demonstrated that knock-out of CALM1 could sensitize ESCC cells to EGFR inhibitor, and it may exert oncogenic role via promotion of EMT. Taken together, CALM1 may be a tempting target to overcome Afatinib resistance.

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