DOI: 10.5061/dryad.2547d7x4g
title: Loss of ICOSL expression in the progression to cervical carcinoma

description: Human papillomavirus (HPV)-related lesions contain types with benign
 outcomes and those with a risk of progression to cancer. We addressed the
 role of immune surveillance in 76 cervical biopsies (normal = 23, HPV+
 benign = 16, HPV+ precancer = 37) by studying the infiltration of
 cytotoxic T cells and the expression of the immune modulators PDL1, ICOSL,
 and miR-155, and compared the data to 101 cervical squamous cell
 carcinomas. In the normal cervix, ICOSL expression was restricted to the
 endocervical epithelia, whereas neither miR-155 nor PDL1 was detected.
 MiR-155 was up-regulated in both the benign (88%) and precancerous (92%)
 HPV squamous intraepithelial lesions (SIL) and co-localized to cells in
 the upper part of the lesion, that is, the area with productive viral
 infection. Both PDL1 (95%) and ICOSL (89%) were only evident in the
 precancerous SIL, and each localized to squamous cells in the basal aspect
 that lacked replicating virus. In both microinvasive and invasive cervical
 squamous cell cancer, miR-155 expression remained high (83%), as did PDL1
 expression (80%), but ICOSL detection was reduced to 17%. Infiltration by
 CD8+ T cells was intense in the invasive lesions, and these cells were
 mostly inactive as determined by the lack of granzyme B co-localization.
 It is concluded that miR-155 expression is a marker of HPV infection in
 both benign and precancerous lesions, whereas approximately 10% of the
 latter lesions that progress to cancer gain PDL1 and lose ICOSL
 expression, which are important factors in avoiding immune surveillance.
description: # Loss of ICOSL expression in the progression to cervical carcinoma
 Dataset DOI: [10.5061/dryad.2547d7x4g](10.5061/dryad.2547d7x4g) ##
 Description of the data and file structure These are original raw images
 used in the "Loss of ICOSL expression in the progression to cervical
 carcinoma manuscript, by Nuovo et al. They are in JPEG format, and the
 name of each file is self-explanatory.  #### Description of the data and
 file structure * The images are of cervical cancer patient samples,
 stained as indicated in their file names. In brief, samples from normal
 (healthy cervix, benign HPV-induced lesion, precancerous HPV-induced
 lesion, or high-grade cervical cancer) were stained for HPV-viral DNA,
 ICOSL, miR-155, ICOS, PDL1, PD1, and CD8, either alone or in co-expression
 analyses.  HPV in situ hybridization for viral RNA was done using the ACD
 RNAscope assay. Co-expression experiments for ICOSL and miR-155 were
 performed by analyzing a given slide with either DAB (brown signal), FAST
 RED (red signal), or NBT/BCIP (blue signal) with the Nuance software used
 for the computer-based quantification analyses. * Data acquisition,
 staining, analyses, and interpretation were supported by CLL Global
 Research Foundation Awards AWD-115284 and AWD-116510 to the senior author
 of this work, Dr. Carlo Croce. * Samples were de-identified, Formalin
 fixed, paraffin paraffin-embedded. Hematoxylin and eosin staining was done
 in each case before immunohistochemistry or in situ hybridization, and the
 diagnosis was confirmed by Dr. Nuovo, the first author in the manuscript,
 a gynecologic pathologist. * All files are in the folder named:
 new_data_for_Gianni.zip