Parallels between Cancer and Infectious Disease

Hotchkiss, Richard S.; Moldawer, Lyle L.

doi:10.1056/nejmcibr1404664

Cited by 170 publications

(164 citation statements)

References 6 publications

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“…The significant decrease in CTLA-4-expressing CD4 + T cells adds support to the important role of this molecule in suppression of immune responses in general and its suggested role in immune hyporesponsiveness induced by helminths (21). When put in the context of the blockade of CTLA-4 (as well as PD-1) in treatment of melanoma and other cancers (22), these findings lend further support to the suggested similarities between immunoregulation in chronic infectious diseases and cancers (23). Three-monthly albendazole treatment over a 2-y period did not eliminate helminths.…”

Section: Discussionsupporting

confidence: 58%

Community deworming alleviates geohelminth-induced immune hyporesponsiveness

Wammes

Hamid

Wiria

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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In cross-sectional studies, chronic helminth infections have been associated with immunological hyporesponsiveness that can affect responses to unrelated antigens. To study the immunological effects of deworming, we conducted a cluster-randomized, double-blind, placebo-controlled trial in Indonesia and assigned 954 households to receive albendazole or placebo once every 3 mo for 2 y. Helminthspecific and nonspecific whole-blood cytokine responses were assessed in 1,059 subjects of all ages, whereas phenotyping of regulatory molecules was undertaken in 121 school-aged children. All measurements were performed before and at 9 and 21 mo after initiation of treatment. Anthelmintic treatment resulted in significant increases in proinflammatory cytokine responses to Plasmodium falciparum-infected red blood cells (PfRBCs) and mitogen, with the largest effect on TNF responses to PfRBCs at 9 moestimate [95% confidence interval], 0.37 [0.21-0.53], P value over time (P time ) < 0.0001. Although the frequency of regulatory T cells did not change after treatment, there was a significant decline in the expression of the inhibitory molecule cytotoxic T lymphocyteassociated antigen 4 (CTLA-4) on CD4 + T cells of albendazoletreated individuals, -0.060 [-0.107 to -0.013] and -0.057 [-0.105 to -0.008] at 9 and 21 mo, respectively; P time = 0.017. This trial shows the capacity of helminths to up-regulate inhibitory molecules and to suppress proinflammatory immune responses in humans. This could help to explain the inferior immunological responses to vaccines and lower prevalence of inflammatory diseases in low-compared with high-income countries.helminths | albendazole | cytokine responses | Indonesia | deworming S oil-transmitted helminths (STHs) represent the most common infectious disease worldwide (1). In addition to specific worm-associated morbidities, it has been argued that chronic STH infections may magnify health-related burdens in communities remote from health care facilities, exacerbating anemia, poor nutritional status, and possibly poor cognitive development (1). However, this was not fully supported by the latest analysis of the Cochrane database (2).Immunologically, cellular immune hyporesponsiveness is a hallmark of chronic helminth infections that may allow parasites' longterm survival (3). The consequences of immunosuppression are manifold with potentially major public health relevance. Immune hyporesponsiveness could curtail effective immune responses, thereby increasing susceptibility to pathogens, and helminths are associated with suboptimal vaccine responses (4-6). The helminthrelated dampened immune responses might nevertheless help to prevent immunopathology during coinfections and, possibly, aberrant reactivity to environmental or self-antigens (7). With respect to the latter, there is currently much interest in the use of helminth infections to treat allergies and autoimmune diseases, exploiting their ability to induce immune hyporesponsiveness (8).Suppressed lymphocyte responses were described in the 19...

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Section: Discussionsupporting

confidence: 58%

Community deworming alleviates geohelminth-induced immune hyporesponsiveness

Wammes

Hamid

Wiria

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Several promising immuno-adjuvant agents are slated for testing in the near future, including GM-CSF (ClinicalTrials.gov identifier: NCT02361528), IL-7, anti-PD-L1 (ClinicalTrials.gov identifier: NCT02576457), and thymosin-alpha-1 [2,8,12,13,16,17]. Given the remarkable success of immunotherapy in cancer and the similarities in the immune defects in cancer and sepsis patients [18], it appears plausible that immunotherapy may represent a major advance in the treatment of this highly lethal disease.…”

Section: How Should Development Of Immunosuppression Impact Clinical mentioning

confidence: 99%

Is this critically ill patient immunocompromised?

2015

Self Cite

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“…Furthermore, persistent inflammation, chronic immobility, catabolic drugs, and extended paralytics all contribute to a protracted state of immune dysregulation and chronic deterioration. Thus, investigators have been forced to refocus their efforts on the underlying innate and adaptive immune derangements that facilitate impaired sepsis recovery and survival, especially over the long term (19,20). In this Review, we will highlight the multitude of sepsis-induced alterations in innate and adaptive immune cell function as well as the clinical implications and potential therapeutic interventions.…”

Section: Introductionmentioning

confidence: 99%

Sepsis-induced immune dysfunction: can immune therapies reduce mortality?

Delano¹,

Ward²

2016

Journal of Clinical Investigation

502

472

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Sepsis affects the immune system by directly altering the lifespan, production, and function of the effector cells responsible for Sepsis is a systemic inflammatory response induced by an infection, leading to organ dysfunction and mortality. Historically, sepsis-induced organ dysfunction and lethality were attributed to the interplay between inflammatory and antiinflammatory responses. With advances in intensive care management and goal-directed interventions, early sepsis mortality has diminished, only to surge later after "recovery" from acute events, prompting a search for sepsis-induced alterations in immune function. Sepsis is well known to alter innate and adaptive immune responses for sustained periods after clinical "recovery," with immunosuppression being a prominent example of such alterations. Recent studies have centered on immune-modulatory therapy. These efforts are focused on defining and reversing the persistent immune cell dysfunction that is associated with mortality long after the acute events of sepsis have resolved.

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Parallels between Cancer and Infectious Disease

Cited by 170 publications

References 6 publications

Community deworming alleviates geohelminth-induced immune hyporesponsiveness

Community deworming alleviates geohelminth-induced immune hyporesponsiveness

Is this critically ill patient immunocompromised?

Sepsis-induced immune dysfunction: can immune therapies reduce mortality?

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