Restoration of CD4+ T Cells during NAFLD without Modulation of the Hepatic Immunological Pattern Is Not Sufficient to Prevent HCC

Madison Isbell; Faridoddin Mirshahi; Hussein F Aqbi; Chunqing Guo; Mulugeta Saneshaw; Nicholas Koelsch; Michael O Idowu; Dana Austin; Cohava Gelber; Xiang-Yang Wang; Arun J Sanyal; Masoud H Manjili

doi:10.3390/cancers14225502

Restoration of CD4⁺ T Cells during NAFLD without Modulation of the Hepatic Immunological Pattern Is Not Sufficient to Prevent HCC

Cancers (Basel). 2022 Nov 9;14(22):5502. doi: 10.3390/cancers14225502.

Authors

Madison Isbell^{1

2}, Faridoddin Mirshahi³, Hussein F Aqbi^{1

4}, Chunqing Guo^{2

5}, Mulugeta Saneshaw³, Nicholas Koelsch^{1

2}, Michael O Idowu^{2

6}, Dana Austin⁷, Cohava Gelber⁷, Xiang-Yang Wang^{2

5}, Arun J Sanyal^{2

3}, Masoud H Manjili^{1

2

6}

Affiliations

¹ Department of Microbiology & Immunology, VCU School of Medicine, Richmond, VA 23298, USA.
² VCU Massey Cancer Center, 401 College Street, Richmond, VA 23298, USA.
³ Department of Internal Medicine, VCU School of Medicine, Richmond, VA 23298, USA.
⁴ College of Science, Mustansiriyah University, Baghdad P.O. Box 14022, Iraq.
⁵ Department of Human & Molecular Genetics, VCU School of Medicine, Richmond, VA 23298, USA.
⁶ Department of Pathology, VCU School of Medicine, Richmond, VA 23298, USA.
⁷ Serpin Pharma, 9501 Discovery Blvd., Suite 120, Manassas, VA 20109, USA.

Abstract

Predominant inflammatory immunological patterns as well as the depletion of CD4⁺ T cells during nonalcoholic fatty liver disease (NAFLD) are reported to be associated with the progression of hepatocellular carcinoma (HCC). Here, we report that an LRP-1 agonistic peptide, SP16, when administered during advanced NAFLD progression, restored the depleted CD4⁺ T cell population but did not significantly affect the inflammatory immunological pattern. This data suggests that restoration of CD4⁺ T cells without modulation of the hepatic immunological pattern is not sufficient to prevent HCC. However, SP16 administered early during NAFLD progression modulated the inflammatory profile. Future studies will determine if regulation of the inflammatory immune response by SP16 early in NAFLD progression will prevent HCC.

Keywords: NAFLD; hepatocellular carcinoma; immunological pattern; inflammation; tumor microenvironment.

Abstract

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