HIV and Cancer Immunotherapy: Similar Challenges and Converging ApproachesSubmit Manuscript on this topic
Antiretroviral therapy (ART) suppresses viral replication in HIV-infected individuals but does not eliminate the reservoir of latently infected cells. Indeed, the virus re-emerges rapidly in large majority of individuals if treatment is stopped. Given the challenge of delivering expensive and potentially harmful ART on a global level, there is great interest in the development of short-term, well-tolerated treatment regimens that will either fully eradicate all HIV (a “cure”) or allow durable control of HIV replication in absence of any therapy (a “remission”). Although both are formidable challenges for HIV treatment, there is enthusiasm for application of a “remission” approach against cancer, driven in part by recent advances in using novel immunotherapies to kill cancer cells and control their spread.
Although cancer and HIV infection are very different diseases, there are interesting parallels between them that could inform and guide the development of immunotherapeutic approaches for the treatment of both conditions. In both diseases, a relatively rare and persistent subset of cells with the capacity to cause harm becomes established. These cells are difficult to distinguish from normal cells and often reside in anatomic locations that are difficult to access. Development of advanced imaging methods to identify and quantify these cells is ongoing in both disciplines. In both settings, the virus or cancer cells exhibit capacity to evolve over time, and the viral reservoirs or cancer cells can remain dormant for many years, before reactivation. Finally, understanding how HIV-infected cells and cancer cells persist is critical for both diseases.
The persistence of HIV-infected or cancer cells is often associated with a chronic inflammatory environment, which eventually results in impaired immune responses. Specifically, upregulation of Tregs’ suppressive function and expression of co-inhibitory receptors on effector T cells, which are physiological protective responses that ensure self-tolerance and avoid excessive inflammation, are paradoxically favoring towards HIV and cancer dissemination. Mechanistic insight into the regulation of these immunosuppressive pathways will thus help in the development of strategies aimed at enhancing the capacity of the immune system to eliminate cancer cells and HIV-harbouring cells.
Since HIV and cancer share similar immune obstacles, they may also share curative or preventive approaches. In this regard, immunotherapies that target the mechanisms underlying impaired immune surveillance have been remarkably successful against cancer. For example, a significant proportion of patients with a history of lethal cancers are now experiencing long-term remission in response to Check Point Inhibitors (CPIs) such as anti-PD-1 and anti-CTLA-4. CPIs are also actively being tested in non-human primate models against HIV infection. However, recent observations in HIV-infected adults with cancer suggest that these approaches are unlikely to cure HIV alone and might have an unacceptable safety profile. Thus, novel strategies with enhanced efficacy and reduced risk that have the potential to work in a similar fashion against both cancer and HIV are being developed. These include: Therapeutic or preventive vaccines; Reduction of residual inflammation; Depletion or reduced function of Tregs; Cytokines and Toll Like Receptor (TLR) agonists; and Gene therapy.
In this Research Topic, we seek Reviews, Mini-Reviews and Original Research articles that discuss the parallels between the immunological mechanisms underlying the pathogenesis and persistence of HIV and cancer. We also aim to discuss how therapeutic approaches aimed at modulating immune surveillance in HIV could be applicable in cancer and vice versa in the hope of accelerating novel and more efficacious treatments for both diseases. Therefore, we welcome studies that seek to either: (i) provide comparisons between HIV and Cancer or (ii) open a discussion on how specific findings could be applicable in either disease (HIV versus Cancer) according to the following sub-topics:
(i) Parallels between the mechanisms underlying cancer and HIV persistence and immune evasion including increased survival, localization, epigenetic modification, chronic inflammation, immunosuppressive responses.
(ii) Parallels between immune responses against the HIV reservoir and cancer cells e.g. Cytotoxic lymphocytes, NK cells, B cells, Treg cells, Mucosal Associated Invariant T (MAIT) cells.
(iii) Recent advances in development of immune therapeutics for the treatment of HIV and cancer including checkpoint blockade, DARTs, CAR T cells, therapeutic vaccines, targeting of Tregs, and cytokines.
(iv) Immunological biomarkers for prediction of HIV and cancer disease progression and response to immune-based interventions.