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. 2024 May;56(5):853-860.
doi: 10.1016/j.dld.2023.09.015. Epub 2023 Oct 14.

Evaluation of immune infiltrate according to the HER2 status in colorectal cancer

Chloé Molimard  1 , Fanny Dor  2 , Alexis Overs  3 , Franck Monnien  2 , Grégoire Gessain  4 , Loïs Kedochim  2 , Flavia D'Angelo  2 , Marine Abad  2 , Morgane Heberle  5 , Valentin Derangère  6 , François Ghiringhelli  7 , Lucine Vuitton  8 , Séverine Valmary-Degano  9 , Christophe Borg  10 , Zaher Lakkis  11 , Fréderic Bibeau  2
Affiliations
Free article

Evaluation of immune infiltrate according to the HER2 status in colorectal cancer

Chloé Molimard et al. Dig Liver Dis. 2024 May.
Free article

Abstract

Background and aims: In colorectal cancer (CRC), HER2 targeting is a promising treatment and immune infiltrate is an important area of research and strategy. Data regarding HER2 status and immune infiltrate are lacking. The aim of this study was to compare the immune infiltrate between HER2 amplified and non-amplified categories in proficient MisMatchRepair (pMMR)/microsatellite stable (MSS) CRC.

Methods: HER2 immunohistochemistry (IHC) and fluorescence in situ hybridization were performed in a retrospective series of 654 CRC. Lymphocyte infiltrate was analysed by anti-CD3, CD8 and CD4 IHC and evaluated digitally using QuPath software.

Results: Among the 654 CRC, we first observed a decreased CD3+ and CD8+ infiltrate between HER2 amplified (all IHC 3+ except one 2+) and non-amplified HER2 2+ IHC CRC (p = 0.059 and 0.072 respectively). A supplementary analysis of 258 pMMR/MSS CRC from the previous cohort, displaying all the IHC scores (0, 1+, 2+, 3+), showed a lower CD3+ infiltrate between HER2 amplified versus HER2 0 (p = 0.002), 1+ (p = 0.088) and non-amplified 2+ (p = 0.081) IHC cases.

Conclusions: Our original findings suggest that in pMMR/MSS CRC, the immune infiltrate is reduced in HER2 amplified versus other HER2 categories. These data might be useful for future strategies combining anti-HER2 treatments and immune checkpoint inhibitors and need to be confirmed in larger CRC cohorts.

Keywords: Colorectal cancer; HER2; Immune infiltrate; QuPath software.

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Conflict of interest statement

Conflict of Interest Chloé Molimard, Fanny Dor, Alexis Overs, Franck Monnien, Grégoire Gessain, Loïs Kedochim, Flavia D'Angelo, Marine Abad, Morgane Heberle, Valentin Derangère, François Ghiringhelli, Lucine Vuitton, Séverine Valmary-Degano, Christophe Borg, Zaher Lakkis, Frédéric Bibeau have no competing financial interests of personal relationships that could have appeared to influence the work reported in this paper.