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. 2024 Dec;20(6):779-788.
doi: 10.1111/ajco.14108. Epub 2024 Sep 4.

Different characteristics of the tumor immune microenvironment among subtypes of salivary gland cancer

Yoshiaki Nagatani  1 , Naomi Kiyota  1   2 , Yoshinori Imamura  1 , Taiji Koyama  1 , Yohei Funakoshi  1 , Masato Komatsu  3 , Tomoo Itoh  3 , Masanori Teshima  4 , Ken-Ichi Nibu  4 , Kazuko Sakai  5 , Kazuto Nishio  5 , Manami Shimomura  6 , Tetsuya Nakatsura  6 , Daiki Ikarashi  6 , Takayuki Nakayama  6 , Shigehisa Kitano  7 , Hironobu Minami  1   2
Affiliations

Different characteristics of the tumor immune microenvironment among subtypes of salivary gland cancer

Yoshiaki Nagatani et al. Asia Pac J Clin Oncol. 2024 Dec.

Abstract

Aim: Although immune checkpoint inhibitors (ICPi) for salivary gland cancer (SGC) have been investigated in clinical trials, details of the tumor immune microenvironment (TIME) remain unclear. This research aimed to elucidate the TIME of SGC and its relationship with tumor mutation burden (TMB) and to explore the rationale for the applicability of ICPi.

Materials and methods: We selected five pathological types, namely adenoid cystic carcinoma (ACC); adenocarcinoma, not otherwise specified (ANOS); salivary duct carcinoma (SDC); and low/high-grade mucoepidermoid carcinoma (MEClow/high). We investigated the TIME and TMB of each pathological type. TIME was evaluated by multiplexed fluorescent immunohistochemistry. TMB was measured by next-generation sequencing.

Results: ACC and MEChigh showed the lowest and highest infiltration of immune effector and suppressor cells in both tumor and stroma. ANOS, SDC, and MEClow showed modest infiltration of immune effector cells in tumors. Correlation analysis showed a positive correlation between CD3+CD8+ T cells in tumor and TMB (r = 0.647). CD3+CD8+ T cells in tumors showed a positive correlation with programmed cell death-ligand 1 expression in tumor cells (r = 0.513) and a weak positive correlation with CD3+CD4+Foxp3+ cells in tumors (r = 0.399). However, no correlation was observed between CD3+CD8+ T cells and CD204+ cells in tumors (r = -0.049).

Conclusion: The TIME of ACC was the so-called immune desert type, which may explain the mechanisms of the poor response to ICPi in previous clinical trials. On the other hand, MEChigh was the immune-inflamed type, and this may support the rationale of ICPi for this pathological subtype.

Keywords: immune checkpoint inhibitor; multiplexed fluorescent immunohistochemistry; salivary gland cancer; tumor immune microenvironment; tumor mutation burden.

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References

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