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

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 MESSAGES TREM-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.

Fibroblasts from HPV-negative oropharynx squamous cell carcinomas stimulate the release of osteopontin from cancer cells via the release of IL-6

“…Interestingly, given the lack of response between the CAFs and HPV-positive cells which we have again demonstrated, many more M1/M2 macrophages (which often express OPN) have been identified in HPV+ stroma, which, if at a high level, has been associated with poor regional control ( 49 ). It has also been demonstrated that macrophages expressing TREM1 are important in the progression of HPV+ OPSCC ( 50 ) and that fibroblasts with a matrix-CAF phenotype collaborate with SPP1-expressing TAMs to promote tumour progression in HNSCC ( 51 ). This may indicate a greater importance in the role of TAMs in the HPV-positive TME, which will require further investigation, as an additional element to the OPSCC-fibroblast model.…”

Prognostic Significance of the Microenvironment in Human Papillomavirus Oropharyngeal Carcinoma: A Systematic Review

“…Using this method, FoxP3+ Treg cells are more likely to be associated with a poor clinical outcome. 10,36,51 Otherwise, conflicting data are due to insufficient analysis of small populations such as NK cells, 70 the significance of tumor-associated macrophages (TAM), 37,44,47,71,72 mast cell infiltration, 27 and monocyte infiltration. 67 All of these markers were investigated in sample sizes ranging from 27 to 168 patients.…”

“…In the case of HPV +OSCC, an anti-HPV T-cell immune response could increase the overall antitumor T-cell response and could contribute to a better clinical outcome. The anti-HPV T-cell specific response has been reported to be associated with the presence of T RM and with a better 71 Ou 2019, 72 Snietura 2020, 37…”

Role of oral microbiome in oral oncogenesis, tumor progression, and metastasis

“…The expression of DNA repair protein, especially the homologous recombination protein RAD51, is upregulated in HPV‐positive HNSCC (Holcomb et al., 2020). TREM‐1 expressed on myeloid cells correlates to HPV‐positive OPSCC progression (Azzimonti et al., 2021). The stimulator of interferon genes is dampened by NLRX1, leading to immune escape in HPV16‐positive HNSCC (Lu et al., 2018; Luo et al., 2020; Shaikh et al., 2019).…”

“…The expression of DNA repair protein, especially the homologous recombination protein RAD51, is upregulated in HPV-positive HNSCC (Holcomb et al, 2020). TREM-1 expressed on myeloid cells correlates to HPV-positive OPSCC progression (Azzimonti et al, 2021).…”