Pathologic Response and Tumor-Infiltrating Lymphocytes during Chemoradiotherapy: Promising Predictive and Prognostic Markers for Chemoradiotherapy Response and Outcome in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma

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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Tumor Infiltrating Lymphocytes and CD8+ T Cell Subsets as Prognostic Markers in Patients with Surgically Treated Laryngeal Squamous Cell Carcinoma

Head and Neck Pathology ◽

10.1007/s12105-019-01101-6 ◽

2019 ◽

Vol 14 (3) ◽

pp. 689-700 ◽

Cited By ~ 2

Author(s):

Kyriakos Chatzopoulos ◽

Vassiliki Kotoula ◽

Kyriaki Manoussou ◽

Konstantinos Markou ◽

Konstantinos Vlachtsis ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

T Cell ◽

Cell Carcinoma ◽

Squamous Cell ◽

Laryngeal Squamous Cell Carcinoma ◽

Prognostic Markers ◽

Tumor Infiltrating Lymphocytes ◽

Cd8 T Cell ◽

T Cell Subsets ◽

Infiltrating Lymphocytes

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The value of intravoxel incoherent motion diffusion-weighted imaging in predicting the pathologic response to neoadjuvant chemotherapy in locally advanced esophageal squamous cell carcinoma

European Radiology ◽

10.1007/s00330-020-07248-z ◽

2020 ◽

Author(s):

Tao Song ◽

Qi Yao ◽

Jinrong Qu ◽

Hongkai Zhang ◽

Yan Zhao ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Neoadjuvant Chemotherapy ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Diffusion Weighted Imaging ◽

Locally Advanced ◽

Pathologic Response ◽

Intravoxel Incoherent Motion ◽

Response To Neoadjuvant Chemotherapy

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Necroptosis in Esophageal Squamous Cell Carcinoma: An Independent Prognostic Factor and Its Correlation with Tumor-Infiltrating Lymphocytes

Cancers ◽

10.3390/cancers13174473 ◽

2021 ◽

Vol 13 (17) ◽

pp. 4473

Author(s):

Takuro Yamauchi ◽

Fumiyoshi Fujishima ◽

Masatoshi Hashimoto ◽

Junichi Tsunokake ◽

Ryujiro Akaishi ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Prognostic Factor ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Therapeutic Efficacy ◽

Tumor Infiltrating Lymphocytes ◽

Independent Prognostic Factor ◽

Biopsy Specimens ◽

Infiltrating Lymphocytes

Necroptosis is a pivotal process in cancer biology; however, the clinical significance of necroptosis in esophageal squamous cell carcinoma (ESCC) has remained unknown. Therefore, in this study, we aimed to verify the potential involvement of necroptosis in the clinical outcome, chemotherapeutic resistance, and tumor microenvironment of ESCC. Mixed lineage kinase domain-like protein (MLKL) and phosphorylated MLKL (pMLKL) were immunohistochemically examined in 88 surgically resected specimens following neoadjuvant chemotherapy (NAC) and 53 pre-therapeutic biopsy specimens, respectively. Tumor-infiltrating lymphocytes (TILs) were also evaluated by immunolocalizing CD3, CD8, and forkhead box protein 3 (FOXP3) in the residual tumors after NAC. High pMLKL status in the post-NAC resected specimens was significantly correlated with worse prognosis in ESCC patients. Multivariate analysis demonstrated that a high pMLKL status was an independent prognostic factor. In pre-NAC biopsy specimens, a high pMLKL status was significantly associated with a lower therapeutic efficacy. CD8+ TILs were significantly lower in the high-pMLKL group. FOXP3+ TILs were significantly higher in both high-MLKL and high-pMLKL groups. We first demonstrated pMLKL status as an independent prognostic factor in ESCC patients. Our study revealed the possible involvement of necroptosis in the immunosuppressive microenvironment, resulting in the attenuated therapeutic efficacy of NAC and eventual adverse clinical outcomes in ESCC.

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