Prognostic markers in oropharyngeal squamous cell carcinoma: focus on CD70 and tumour infiltrating lymphocytes.

We evaluated the expression of CD70 as biomarker for prognosis in patients with oropharyngeal squamous cell carcinoma (OSCC). We also examined the prognostic value of tumour infiltrating lymphocytes (TILs) in our study cohort. Formalin fixed, paraffin embedded tissue originating from the oropharynx of 78 patients was immunohistochemically stained for CD70, CD3, CD8 and FoxP3. Expression of CD70, CD3, CD8, FoxP3 and HPV status was correlated with clinicopathological characteristics. Overall survival (OS) was determined by a log-rank (Mantel-Cox) test whereas the Cox proportional hazard model was used for multivariate analysis. CD70 expression demonstrated no influence on OS. Tumours heavily infiltrated by TILs were linked with better outcome, for the total number of TILs as well as for the CD3+ and CD8+ T cell count. A Cox proportional hazard model proved that solely CD8+ infiltrating T cells exhibit a positive effect on OS (HR=0.30, 95% confidence interval 0.13-0.72). Our results demonstrate that CD8+ TILs constitute an independent prognosticator in patients diagnosed with OSCC. Further validation of the prognostic value of CD8+ TILs in OSCC is warranted and could provide us with a better insight into the immunological status of these malignancies.

De Meulenaere A ，Vermassen T ，Aspeslagh S ，Zwaenepoel K ，Deron P ，Duprez F ，Rottey S ，Ferdinande L ... -  《-》

Prognostic significance of tumor infiltrating immune cells in oral squamous cell carcinoma.

Fang J ，Li X ，Ma D ，Liu X ，Chen Y ，Wang Y ，Lui VWY ，Xia J ，Cheng B ，Wang Z ... -  《BMC CANCER》

CD8+ tumour-infiltrating lymphocytes in relation to HPV status and clinical outcome in patients with head and neck cancer after postoperative chemoradiotherapy: A multicentre study of the German cancer consortium radiation oncology group (DKTK-ROG).

We examined the prognostic value of tumour-infiltrating lymphocytes (TILs) in patients with squamous cell carcinoma of the head and neck (SCCHN) after surgery and postoperative cisplatin-based chemoradiotherapy. FFPE-tissue originating from the surgery of 161 patients treated in 8 DKTK partner sites was immunohistochemically stained for CD3 and CD8. Their expression was correlated with clinicopathological characteristics as well as overall survival (OS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS), also in the context of the HPV16-DNA/p16 status. After a median follow-up of 48 months (range: 4100 months), OS at 4 years was 46.5% for the entire cohort. In multivariate analysis, high CD8 expression was confirmed as an independent prognostic parameter for OS (p = 0.002), LPFS (p = 0.004) and DMFS (p = 0.006), while CD3 expression lacked significance. In multivariate analysis HPV16 DNA positivity was associated with improved OS (p = 0.025) and LPFS (p = 0.013) and p16-positive patients showed improved DMFS (p = 0.008). Interestingly, high CD8 expression was a prognostic parameter for the clinical outcome in both HPV16 DNA-positive and HPV16 DNA-negative patients. Similar findings were observed in the multivariate analysis for the combined HPV16 DNA/p16 status. Altogether, CD8+ TILs constitute an independent prognostic marker in SCCHN patients treated with adjuvant chemoradiotherapy. These data indicate that CD8-positive TILs have antitumour activity and could be used for treatment stratification. Further validation of the prognostic value of CD8+ TILs as a biomarker and its role in the immune response in SCCHN patients after adjuvant chemoradiotherapy is warranted and will be performed in the prospective DKTK-ROG study.

Balermpas P ，Rödel F ，Rödel C ，Krause M ，Linge A ，Lohaus F ，Baumann M ，Tinhofer I ，Budach V ，Gkika E ，Stuschke M ，Avlar M ，Grosu AL ，Abdollahi A ，Debus J ，Bayer C ，Stangl S ，Belka C ，Pigorsch S ，Multhoff G ，Combs SE ，Mönnich D ，Zips D ，Fokas E ... -  《-》

CD8+ and CD4+ tumour infiltrating lymphocytes in relation to human papillomavirus status and clinical outcome in tonsillar and base of tongue squamous cell carcinoma.

Patients with human papillomavirus (HPV) positive tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC, respectively) have a better clinical outcome than those with HPV negative tumours, irrespective of treatment. However, to better individualise treatment, additional biomarkers are needed together with HPV status. In a pilot study, we showed that high numbers of CD8(+) tumour infiltrating lymphocytes (TILs) in HPVDNA+ p16(INK4a+) TSCC indicated a better outcome. Here this study was extended. Totally 203 TSCC and 77 BOTSCC formalin fixed paraffin embedded tumour biopsies, earlier tested for HPV DNA (79% HPVDNA+) and p16(INK4a) from patients treated with curative intention, were analysed for CD8(+) and CD4(+) TILs by immunohistochemistry. Data obtained for 275 patients were correlated to HPVDNA and p16(INK4a) status, overall survival (OS) and disease free survival (DFS). In both HPVDNA+ and HPVDNA+ p16(INK4a+) tumours higher CD8(+) TIL counts correlated to a better 3-year OS (logrank test, both p<0.001) and 3-year DFS (logrank test, p = 0.003 and p = 0.004 respectively) as compared to the lowest quartile in the groups. A similar pattern was observed when analysing TSCC alone, while for BOTSCC significance was obtained only for 3-year OS. In HPVDNA- tumours the trend was similar, but significance was obtained again only for 3-year OS. The number of CD4(+) TILs did not generally correlate to survival. In conclusion, in HPVDNA+ and/or HPVDNA+ p16(INK4a+) tumours high CD8(+) TIL counts indicated a better 3-year OS. This suggests that high CD8(+) TIL counts together with HPVDNA+ or HPVDNA+ p16(INK4a+) could be used when selecting patients for more individualised treatment.

Nordfors C ，Grün N ，Tertipis N ，Ährlund-Richter A ，Haeggblom L ，Sivars L ，Du J ，Nyberg T ，Marklund L ，Munck-Wikland E ，Näsman A ，Ramqvist T ，Dalianis T ... -  《-》

Density and location of CD3(+) and CD8(+) tumor-infiltrating lymphocytes correlate with prognosis of oral squamous cell carcinoma.

Tumor-infiltrating lymphocytes (TILs) are regarded as adaptive immune response of the host to cancer cells and valuable prognostic factors. Here, we sought to characterize the densities and locations of CD3+ and CD8+ TILs in primary oral squamous cell carcinoma (OSCC) samples and assess their clinicopathological and prognostic significance. A total number of 169 OSCC samples from 2 independent patient cohorts (Nanjing cohort, 93 cases; Wuxi cohort, 76 cases) were retrospectively collected. The numbers of CD3+ and CD8+ TILs at tumor center (CT) and invasive margin (IM) of OSCC were identified by immunohistochemistry and calculated. The optimal cutoff values for CD3+ and CD8+ TILs to stratify patients were determined by X-tile software in Nanjing cohort and further utilized in Wuxi cohort. The associations between CD3+ /CD8+ TILs and clinicopathological parameters or patient survival were assessed. The prognostic values of CD3+ / CD8+ TILs were evaluated by Cox regression analyses. CD3+ and CD8+ TILs were identified at both CT and IM and enriched at IM. High density of CD3+ TILs at IM (CD3 IM) was significantly associated with increased overall and disease-specific survival (P < .05). High density of CD8+ TILs at CT (CD8 CT) was significantly associated with increased overall but not disease-specific survival. Moreover, CD3 IM and CD8 CT were identified as independent prognostic factors for patient survival. Our findings provide further evidence to support the prognostic values of CD3+ and CD8+ TILs for OSCC, suggesting that TIL subsets might be viable biomarkers and therapeutic targets with translational significance.

Zhou C ，Wu Y ，Jiang L ，Li Z ，Diao P ，Wang D ，Zhang W ，Liu L ，Wang Y ，Jiang H ，Cheng J ，Yang J ... -  《-》