Tumor-infiltrating lymphocytes associate with outcome in nonendemic nasopharyngeal carcinoma: a multicenter study

Almangush, Alhadi; Ruuskanen, Miia; Hagström, Jaana; Hirvikoski, Pasi; Tommola, Satu; Kosma, Veli‐Matti; Nieminen, Pentti; Mäkitie, Antti; Leivo, Ilmo

doi:10.1016/j.humpath.2018.07.009

Cited by 35 publications

(39 citation statements)

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“…We found that stromal categorization that was based on the assessment of tumor-stroma ratio and stromal TILs can serve as a robust tool for prognostication of early OTSCC. Importantly, these two stromal characteristics have shown promising prognostic significance in different subsites of the head and neck cancer [15,[25][26][27][28][29]. We noted that the combination score has a prognostic value superior to each of the single parameters separately (Table 1).…”

Section: Discussionmentioning

confidence: 87%

Stromal categorization in early oral tongue cancer

et al. 2020

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Stromal categorization has been used to classify many epithelial cancer types. We assessed the desmoplastic reaction and compared its significance with other stromal characteristics in early (cT1-2N0) oral tongue squamous cell carcinoma (OTSCC). In this multi-institutional study, we included 308 cases treated for early OTSCC at five Finnish university hospitals or at the A.C. Camargo Cancer Center in São Paulo, Brazil. The desmoplastic reaction was classified as immature, intermediate, or mature based on the amount of hyalinized keloid-like collagen and myxoid stroma. We compared the prognostic value of the desmoplastic reaction with a stromal grading system based on tumor-stroma ratio and stromal tumor-infiltrating lymphocytes. We found that a high amount of stroma with a weak infiltration of lymphocytes was associated statistically significantly with a worse disease-free survival with a hazard ratio (HR) of 2.68 (95% CI 1.26–5.69), worse overall survival (HR 2.95, 95% CI 1.69–5.15), and poor disease-specific survival (HR 2.66, 95% CI 1.11–6.33). Tumors having a high amount of stroma with a weak infiltration of lymphocytes were also significantly associated with a high rate of local recurrence (HR 4.13, 95% CI 1.67–10.24), but no significant association was found with lymph node metastasis (HR 1.27, 95% CI 0.37–4.35). Categorization of the stroma based on desmoplastic reaction (immature, intermediate, mature) showed a low prognostic value for early OTSCC in all survival analyses (P > 0.05). In conclusion, categorization of the stroma based on the amount of stroma and its infiltrating lymphocytes shows clinical relevance in early OTSCC superior to categorization based on the maturity of stroma.

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Section: Discussionmentioning

confidence: 87%

Stromal categorization in early oral tongue cancer

et al. 2020

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“…Recently, there is a worldwide research effort to standardize determination of TILs. Many studies have reported that a strong lymphocytic infiltration associates with favorable clinical outcome of different tumors including those of head and neck [18][19][20] . Such favorable outcome could be due to the destruction of cancer cells and anti-tumor effect of the immune response 21 .…”

Section: Discussionmentioning

confidence: 99%

Assessment of Tumor-infiltrating Lymphocytes Predicts the Behavior of Early-stage Oral Tongue Cancer

Heikkinen

Bello

Wahab

et al. 2019

American Journal of Surgical Pathology

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Tumor-infiltrating lymphocytes (TILs) have shown a promising prognostic value in many epithelial cancers. We sought to assess the prognostic value of TILs in a multicenter cohort of early oral tongue squamous cell carcinoma (OTSCC). The percentage of TILs was assessed on the surgical resection slides stained wit h hematoxylin and eosin (HE). The assessment of TILs was performed in the stromal compartment and in the intra-epithelial compartment (at the invasive front and at the center of the tumor). We followed the method that was described recently by the International Immuno-Oncology Biomarker Working Group for the assessment of TILs. A total of 308 cases from the five Finnish university hospitals and from A.C. Camargo Cancer Center, São Paulo, Brazil were included. We found a promising prognostic value for stromal TILs at the invasive front in the multivariable analysis with a hazard ratio of 2.61 (95%CI 1.77-3.83; P<0.001) for overall survival, 1.99 (95%CI 1.07-3.69; P=0.040) for disease-specific survival, and 1.94 (95%CI 1.14-3.29; P=0.020) for disease-free survival. In conclusion, evaluation of TILs is simple and can aid in identifying the high-risk cases of early OTSCC. The method introduced by the International Immuno-Oncology Biomarker Working Group can be used for standardized determination of TILs in early OTSCC.

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“…Abbreviations: (+ and -) are number of positive and negative patients, *P values in bold represent significant data as calculated using χ 2 or Fisher's Exact Tests, ♣ Numbers between brackets are the percentages of patients Several studies have shown the prognostic value of TIL in various types of solid tumors [9], including Head and Neck cancers [10], and more specifically, NPC [11][12][13][14], although their studies were not devoted to LA-NPC. Wang et al [13] and Almangush et al [15] have studied total TIL in NPC using H&E stained sections and found a high correlation between total TIL and disease outcome using a large cohort (1490 patients). On the other hand, Zhu et al [14], Lu et al [11], and Ono et al [12] investigated specific TIL like CD3+ and/or CD8+ TIL on survival of NPC.…”

Section: Discussionmentioning

confidence: 99%

CD3+T-lymphocyte infiltration is an independent prognostic factor for advanced nasopharyngeal carcinoma

et al. 2020

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Background: Locally advanced nasopharyngeal carcinoma (LA-NPC) is a relatively rare disease in the west but more common in East Asia and areas of the Middle East like Saudi Arabia. Despite the advances in radiation therapy techniques, some patients relapse after treatment. In the coming era of cancer immunotherapy, prognostic factors for LA-NPC need to be further defined using immune-relevant markers. Several markers are available; however, the most robust and accessible/affordable marker is not well-defined. Methods: Retrospectively, tumor-infiltrating lymphocytes (TIL), their subsets as well as tumoral PD-L1 expression were analyzed in tumor tissues from 63 LA-NPC patients treated with platinum-based concurrent chemo-radiotherapy (CCRT) in addition to 20 cases with metastatic (MET) disease. Immunostaining was done using a validated and fully automated system. Scoring was done by two independent pathologists and results were compared.Results: There was no statistical difference between LA-NPC and MET disease in terms of CD3+, CD8+ TIL infiltration, or tumoral PD-L1 expression. In LA-NPC, low CD3+ TIL infiltration highly correlated with shorter disease-free survival (DFS, HR = 8.5, p = < 0.001) and overall survival (OS, HR = 13, p = 0.015) with substantial agreement between scoring pathologists. A similar correlation was found between low CD8+ TIL and survival. Correlation of total TIL was significant with DFS (HR = 4.0, p = 0.008), borderline with OS and the correlation was dependent on the scoring pathologist. Having histological WHO type I&II correlated significantly with shorter DFS (HR 4.03, p = 0.008) and low CD3+ TIL (p = 0.009). Subgroup analysis of LA-NPC that included undifferentiated type (WHO type III) cases only (n = 58), showed a strong correlation between low CD3+ TIL and shorter DFS (HR = 7.2, p = < 0.001) and OS (HR = 17.3, p = 0.008). PD-L1 was expressed in 72% of type III LA-NPC cases while lacking PD-L1 expression correlated with shorter OS (HR = 6.1, p = 0.031). Patients with a combination of low CD3+ TIL and lack of PD-L1 expression had the worst OS (p < 0.001). Conclusions: CD3+ TIL is promising as a robust and independent prognostic marker for DFS and OS of LA-NPC patients treated with platinum-based CCRT. We would suggest the use of CD3 + TIL as a stratifying factor for LA-NPC, which warrants further validation in prospective trials.

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Tumor-infiltrating lymphocytes associate with outcome in nonendemic nasopharyngeal carcinoma: a multicenter study

Cited by 35 publications

References 35 publications

Stromal categorization in early oral tongue cancer

Stromal categorization in early oral tongue cancer

Assessment of Tumor-infiltrating Lymphocytes Predicts the Behavior of Early-stage Oral Tongue Cancer

CD3+T-lymphocyte infiltration is an independent prognostic factor for advanced nasopharyngeal carcinoma

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