Tertiary lymphoid structures associate with improved survival in early oral tongue cancer

Abstract

Background The clinical significance of tertiary lymphoid structures (TLSs) is not well-documented in early oral tongue squamous cell carcinoma (OTSCC). Methods A total of 310 cases of early (cT1-2N0) OTSCC were included in this multicenter study. Assessment of TLSs was conducted on hematoxylin and eosin-stained sections. TLSs were assessed both in the central part of the tumor and at the invasive front area. Results The presence of TLSs associated with improved survival of early OTSCC as presented by Kaplan–Meier survival analyses for disease-specific survival (P = 0.01) and overall survival (P = 0.006). In multivariable analyses, which included conventional prognostic factors, the absence of TLSs associated with worse disease-specific survival with a hazard ratio (HR) of 1.96 (95% CI 1.09–3.54; P = 0.025) and poor overall survival (HR 1.66, 95% CI 1.11–2.48; P = 0.014). Conclusion Histological evaluation of TLSs predicts survival in early OTSCC. TLSs showed superior prognostic power independent of routine WHO grading and TNM staging system.

Architecture of head and neck squamous cell carcinoma tumor microenvironment revealed: can tertiary lymphoid structures predict post-surgery recurrence?

“…Their analysis revealed an association between increased expression levels of CD38 and CD31 in tumors and improved disease-specific survival. In agreement, a multicenter study involving 310 cases of HNSCC have shown the predictive potential of TLSs for patient survival, regardless of TNM stage ( 18 ). It is important to note that a previous landmark study utilizing CODEX also identified CNs resembling TLSs in colorectal cancer patients, which were likewise found to be associated with improved prognosis when localized to the tumor invasive front ( 19 ).…”

Tertiary lymphoid structures in tongue cancer: Association with clinicopathological parameters, preoperative S‐1 chemotherapy response, and prognosis

“…In the present study, the presence or absence of TLSs had no particular effect on the prognosis of recurrence, perhaps because the proportion of cases positive for TLSs was lower than in previous reports on oral cancer. [6][7][8][9] In two recent studies of tongue cancer, 6,7 TLSs were associated with a favorable prognosis. In our cohort, many cases were treated with preoperative chemotherapy, and the overall prognosis was good.…”

“…The presence of TLSs has been regarded as a favorable marker of responsiveness to immune checkpoint blockade therapy in several cancers 1,3 . In addition, in oral cancers, several studies evaluated the presence of TLSs and its prognostic value and reported that patients with TLSs had a good prognosis 6–10 …”

“…1,3 In addition, in oral cancers, several studies evaluated the presence of TLSs and its prognostic value and reported that patients with TLSs had a good prognosis. [6][7][8][9][10] S-1 (Taiho Pharmaceutical Co. Ltd., Tokyo, Japan) is an oral anticancer agent comprising tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate at a molar ratio of 1:0.4:1. Tegafur is a prodrug of 5-fluorouracil (5-FU), and 5-chloro-2,4-dihydroxypyridine enhances the serum 5-FU concentration through competitive inhibition of dihydropyrimidine dehydrogenase, an enzyme responsible for 5-FU catabolism.…”