Lymphocytes Infiltration and Expression of PD-1 and PD-L1 in Colorectal Cancer Between HIV-Infected and Non-HIV-Infected Patients: A Propensity Score Matched Cohort Study

Abstract

BackgroundTumor-infiltrating lymphocytes (TILs) and expression of programmed cell death 1 (PD-1)/programmed death ligand-1 (PD-L1) are crucial for antitumor immunity. However, the status remains undetermined in HIV-infected colorectal cancer (CRC), limiting the use of immunotherapy in HIV-infected CRC patients.MethodsWe examined 27 HIV-infected patients and 120 non-HIV-infected patients with CRC from 2015-2020 at Shanghai Public Health Clinical Center. After matching the propensity score, 13 paired patients in the two groups were also compared. The expression of PD-1/PD-L1 as well as tumor-infiltrating CD4, CD8, and CD56 immune cells was examined using multiplex immunofluorescent analysis. The cell density for positive staining was calculated (cells/mm2) and compared between HIV-infected and non-HIV-infected groups. In addition, the co-expression of PD-1 on immune cells and PD-L1 on tumor cells was compared in these two groups.ResultsThe mean densities of tumor-infiltrating CD4, CD8, CD56 immune cells were 620.2, 261.2, and 0.2 cells/mm2, respectively, in HIV-infected colorectal tumors compared with 698.6, 243, and 14 cells/mm2 in non-HIV-infected tumors. PD-1 expression was 227 cells/mm2 in HIV-infected tumors and 365.2 cells/mm2 in non-HIV-infected tumors. Besides, PD-L1 expression was 108.5 cells/mm2 in HIV-infected tumors and 126.8 cells/mm2 in non-HIV-infected tumors, and no significant difference was found between the two groups. Similarly, there were no significant differences in the expression of PD-1 on TILs and PD-L1 on tumor cells.ConclusionHIV-infected CRC patients had similar tumor-infiltrating lymphocytes (CD4 and CD8 T cells) compared to non-HIV-infected controls and substantially similar PD-1 expression on TILs and PD-L1 expression on tumors. These results support the inclusion of HIV-infected CRC patients in future immunotherapy trials.

Higher Neutrophil-to-Lymphocyte Ratio (NLR) Is a Preoperative Inflammation Biomarker of Poor Prognosis in HIV-Infected Patients with Colorectal Cancer: A Retrospective Study

“…Although our previous study found no diference in immune checkpoint expression between HIV-infected CRC and normal patients [13], these controversial clinical fndings suggest a need for more interest in the relationship between HIV-associated immunodefciency and CRC development. However, some systematic reviews have discovered that PLWH with colorectal cancer are less likely to receive cancer screening or regular treatment, resulting in higher mortality rates than HIV-negative patients [26,27].…”

“…Te three-year overall survival (OS) rate in this cohort was only 55%, which is far below the average [1]. Additionally, our previous study found that colorectal cancer patients with HIV were more likely to be diagnosed at an advanced stage than CRC patients without HIV [13]. Terefore, simple and easily achievable prognostic predictors for patients with HIVinfected CRC are required.…”

“…Although cARTs do not completely eradicate HIV, continued treatment can restore the immune system function [12]. A previous study also found no diference in tumor-infltrating lymphocytes between HIV-positive and HIV-negative CRC patients [13]. Assessing systemic infammation biomarkers in CRC may be aided by studying immune reconstitution in HIV-infected patients.…”

The programed death‐1/programed death ligand‐1 axis and its potential as a therapeutic target for virus‐associated tumours

“…Cao et al 129 examined PD-1/PD-L1 expression and tumourinfiltrating CD4, CD8, and CD56 immune cells in HIV-infected and non-HIV-infected colorectal cancer patients, and found that HIV infection was similar to tumour-infiltrating lymphocytes (TILs) (CD4, CD8 T cells) in non-HIV-infected patients. PD-1 expression on TILs was similar to PD-L1 on tumours, while no significant immunosuppression was detected in the tumour microenvironment of patients LI ET AL.…”

Assessment of the safety of nivolumab in people living with HIV with advanced cancer on antiretroviral therapy: the AIDS Malignancy Consortium 095 Study

“…23,24 However, other groups have found that colorectal cancer and lung cancer in PLWH have similar PD-L1 expression and PD-1 expression of tumor-infiltrating lymphocytes. 25,26 Another objective of this study was to evaluate the effect of nivolumab on CD4/C8 populations and HIV viral load. We found that A previously reported analysis including this cohort showed that nivolumab had no effect on HIV latency or the latent HIV reservoir.…”