Macrophages expressing TREM-1 are involved in the progression of HPV16-related oropharyngeal squamous cell carcinoma

Ann Med. 2021 Dec;53(1):541-550. doi: 10.1080/07853890.2021.1905872.

Abstract

Introduction: Many types of research have been performed to improve the diagnosis, therapy, and prognosis of oropharyngeal carcinomas (OP-SCCs). Since they arise in lymphoid-rich areas and intense lymphocytic infiltration has been related to a better prognosis, a TREM-1 putative function in tumour progression and survival has been hypothesized.

Materials and methods: Twenty-seven human papillomavirus (HPV) 16+ OP-SCC specimens have been analyzed to relate TREM-1 expression with histiocytic and lymphocytic markers, HPV presence and patients' outcome.

Results: No differences have been shown between intratumoral and stromal CD4+ cells, while intratumoral CD8+ lymphocytes are higher with respect to the tumour stroma (p = .0005). CD68+ cells are more than CD35+ and TREM-1+; their presence is related to CD35± and TREM-1± histiocytes (p = .005 and .026, respectively). Intratumoral CD4+ lymphocytes are higher in p16+ cases (11/27) than in p16- (p = .042); moreover, p16 positivity correlates to a better survival (p = .034). CD4+, CD8+ and CD35+ cells have no impact on survival, while CD68 expression heavily influences progression and bad outcome (p = .037). TREM-1 positivity also leads to worst overall survival (p = .001): peritumoral expression and death-cause relationship are always significant, particularly when the cause is OP-SCC (p = .000).

Conclusion: While p16 shows to better stratify HPV16+ patients' outcome, TREM-1+ macrophages suggest their key importance in HPV-related OP-SCCs progression.KEY MESSAGESTREM-1 positivity correlates to the worst overall survival of HPV16-positive OPSCCs-affected patients.p16-positive HPV16 related OPSCCs patients have a better prognosis with respect to p16-negative ones.

Keywords: Human papillomavirus (HPV); oropharyngeal squamous cell carcinoma (OP-SCCs); peritumoral and intratumoral infiltration; triggering receptor expressed on myeloid cells-1 (TREM-1); tumoral microenvironment (TME).

MeSH terms

  • Adult
  • Aged
  • Disease Progression
  • Female
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / virology
  • Human papillomavirus 16*
  • Humans
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • Papillomavirus Infections / genetics*
  • Papillomavirus Infections / virology
  • Prognosis
  • Retrospective Studies
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / virology
  • Triggering Receptor Expressed on Myeloid Cells-1 / metabolism*

Substances

  • Triggering Receptor Expressed on Myeloid Cells-1