Low density of CD3+, CD4+ and CD8+ cells is associated with increased risk of relapse in squamous cell cervical cancer

Nedergaard, Bettina; Ladekarl, Morten; Thomsen, Henrik F.; Nyengaard, Jens Randel; Nielsen, Karsten

doi:10.1038/sj.bjc.6604001

Cited by 75 publications

(68 citation statements)

References 18 publications

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“…Having a high number of CD8 + TILs has been shown to correlate to a favourable clinical outcome in several cancer types, including tonsillar and base of tongue SCC (18,(28)(29)(30). Here this also applied to the combined 2000-2013 HNCUP cohort.…”

Section: Discussionmentioning

confidence: 99%

Validation of Human Papillomavirus as a Favourable Prognostic Marker and Analysis of CD8+ Tumour-infiltrating Lymphocytes and Other Biomarkers in Cancer of Unknown Primary in the Head and Neck Region

Sivars¹,

Landin²,

Grün³

et al. 2017

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Abstract. Background: Human papillomavirus (HPV) is a favourable prognostic factor in oropharyngeal cancer. Moreover, we and others reported that HPV-positive cancer of unknown primary in the head and neck region (HNCUP) has better outcome than HPVHead and neck squamous cell carcinoma (HNSCC), including cancer of the pharynx, larynx, oral cavity, nose and nasal sinuses, often presents as a lump in the neck, and the specific site of the primary tumour is in general revealed after subsequent diagnostic procedures. However, in 2-9% of the cases the primary tumour is not found and the condition is denoted as cancer of unknown primary in the head and neck region (HNCUP) (1). Treatment of the latter has traditionally comprised of neck dissection followed by postoperative oncological treatment, i.e. radiotherapy, at times with the addition of platinum-based chemotherapy or cetuximab, while today in some cases only oncological treatment is given (2).Human papillomavirus (HPV)-associated oropharyngeal SCC is a HNSCC subset dominated by tonsillar and base of tongue SCC (3, 4). HPV-positive tonsillar and base of tongue SCC have increased in incidence in the past decades in the developed world and have better clinical outcomes than HNSCC in general [~80% vs. 40% 5-year overall survival (OS)] (5-8). HPV is frequently found in HNCUP and such cases likely have an HPV-positive oropharyngeal SCC origin, which gives reasons for steering diagnostic procedures as well as radiotherapy towards the oropharynx (9-11).Treatment de-escalation may be attainable in patients with HPV-positive HNCUP, similar to that discussed for patients with HPV-positive oropharyngeal SCC (12). Still, before HPV status of HNCUP can be used to guide treatment, more knowledge on the biology and clinical behaviour of the 665 Τhis article is freely accessible online.

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Section: Discussionmentioning

confidence: 99%

Validation of Human Papillomavirus as a Favourable Prognostic Marker and Analysis of CD8+ Tumour-infiltrating Lymphocytes and Other Biomarkers in Cancer of Unknown Primary in the Head and Neck Region

Sivars¹,

Landin²,

Grün³

et al. 2017

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“…A significantly lower number of CD4 1 TILs was observed in the deceased group than in the surviving group (26.33611 A low density of CD3 1 , CD4 1 and CD8 1 cells is associated with an increased risk of relapse in squamous cell cervical cancer, while a high density of all three cell types is associated with a decreased risk of relapse. 42 High numbers of CD4 1 TILs have also been observed as a favorable prognostic marker in other human cancers such as nonsmall cell lung cancer 36 and head and neck cancer. 43 The characteristics of CD4 1 Tregs and the mechanisms leading to their biological effects remain the subject of extensive investigation.…”

Section: Comparative Numbers Of Cd4mentioning

confidence: 99%

A reversed CD4/CD8 ratio of tumor-infiltrating lymphocytes and a high percentage of CD4+FOXP3+ regulatory T cells are significantly associated with clinical outcome in squamous cell carcinoma of the cervix

et al. 2010

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In this study, 40 biopsy samples collected from cervical cancer patients at the First Affiliated Hospital of Xi'an Jiaotong University, China, were retrospectively assessed using immunohistochemistry for CD4 1 and CD8 1 tumor-infiltrating lymphocytes (TILs) and were analyzed for the expression of FOXP3, OX40, granzyme B (GrB) and perforin (Prf). The proliferating index of the TILs was determined by assessing Ki67 expression. We determined the prognostic value of low and high numbers of TILs on survival by performing KaplanMeier analysis using median values as the cut-off points. Except for the number of CD4 1 FOXP3 1 regulatory T cells (Tregs) and the CD4/ CD8 ratio, none of the CD4 1 , CD8 1 , OX40 1 , GrB 1 or Prf 1 TILs were associated with the overall 5-year survival rate. The 5-year survival rate was significantly lower in patients who had a high percentage of Tregs as compared with the those who had a lower percentage (35.3% versus 88.9%, P50.001), while the 5-year survival rate was significantly higher in patients with a high CD4/CD8 ratio as compared with patients who had a low CD4/CD8 ratio (82.4% versus 44.4%, P50.029). When we considered the deaths and surviving cases as separate groups, we found that both the number of CD4 1 T cells and the CD4/CD8 ratio were significantly lower in patients who died as compared with those who survived (26.33611.80 versus 47.79638.18, P50.023 and 0.6060.25 versus 1.1761.02, P50.019, respectively). In conclusion, decreased proportions of tumor-infiltrating CD4 1 T cells with high percentages of Tregs and reversed CD4/CD8 ratios were significantly associated with the clinical outcome of patients with cervical carcinoma.

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“…[7][8][9][10] For example, TILs are often observed in many types of solid tumors; in some cases they are considered to reflect the host immune system that responds to and eliminates the tumor cells. In fact, higher TIL infiltration has been reported to correlate with better prognosis in many tumor types, [11][12][13][14][15] including ovarian cancer for which a high degree of intratumoral CD8 C T cell was correlated with better clinical response to platinum agents. 16 However, in some cases they may protect cancer cells from the host immune system.…”

Section: Introductionmentioning

confidence: 99%

Characterization of T cell repertoire of blood, tumor, and ascites in ovarian cancer patients using next generation sequencing

et al. 2015

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Tumor-infiltrating lymphocytes (TILs) play an important role in regulating the host immune response and are one of key factors in defining tumor microenvironment. Some studies have indicated that T cell infiltration in malignant ascites is associated with clinical outcome, but few studies have performed detailed characterization of T cell diversity or clonality in malignant effusions. We have applied a next generation sequencing method to characterize T cell repertoire of a set of primary cancers, ascites, and blood from 12 ovarian cancer patients and also analyzed the T cell subtype populations in malignant fluids from 3 ovarian cancer patients. We observed enrichment of certain T cells in tumors and ascites, but most of the enriched T cell receptor (TCR) sequences in tumors and ascites were not common. Moreover, we analyzed TCR sequences of T cell subtypes (CD4 C , CD8 C , and regulatory T cells) isolated from malignant effusions and also found clonal expansion of certain T cell populations, but the TCR sequences were almost mutually exclusive among the three subgroups. Although functional studies of clonally expanded T cell populations are definitely required, our approach offers a detailed characterization of T cell immune microenvironment in tumors and ascites that might differently affect antitumor immune response.

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Low density of CD3+, CD4+ and CD8+ cells is associated with increased risk of relapse in squamous cell cervical cancer

Cited by 75 publications

References 18 publications

Validation of Human Papillomavirus as a Favourable Prognostic Marker and Analysis of CD8+ Tumour-infiltrating Lymphocytes and Other Biomarkers in Cancer of Unknown Primary in the Head and Neck Region

Validation of Human Papillomavirus as a Favourable Prognostic Marker and Analysis of CD8+ Tumour-infiltrating Lymphocytes and Other Biomarkers in Cancer of Unknown Primary in the Head and Neck Region

A reversed CD4/CD8 ratio of tumor-infiltrating lymphocytes and a high percentage of CD4+FOXP3+ regulatory T cells are significantly associated with clinical outcome in squamous cell carcinoma of the cervix

Characterization of T cell repertoire of blood, tumor, and ascites in ovarian cancer patients using next generation sequencing

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