# Obstructive sleep apnea as a modifier of endocrine toxicities associated with immune checkpoint inhibitors in lung cancer

**Authors:** Lucrezia Pisanu, Pasquale Tondo, Francesco Bertuccio, Valentina Conio, Maria Arminio, Klodjana Mucaj, Elisabetta Gallo, Simone Montini, Jessica Saddi, Salvatore Corallo, Angelo G. Corsico, Giuseppe Insalaco, Maria Pia Foschino Barbaro, Giulia Scioscia, Francesco Fanfulla, Vito D’Agnano, Fabio Perrotta, Donato Lacedonia, Giulia M. Stella

PMC · DOI: 10.3389/fimmu.2026.1741875 · Frontiers in Immunology · 2026-02-10

## TL;DR

This paper discusses how obstructive sleep apnea may affect endocrine side effects of immunotherapy in lung cancer patients.

## Contribution

The paper highlights the novel clinical relevance of managing obstructive sleep apnea in lung cancer patients receiving immunotherapy.

## Key findings

- OSA is linked to metabolic and endocrine changes that may interact with immunotherapy.
- Proper OSA management could improve immunotherapy outcomes in lung cancer patients.
- There is a need for further research on OSA's role in cancer treatment.

## Abstract

Obstructive sleep apnea (OSA) is one of the most common sleep disorders in the general population. It is characterized by recurrent alterations in nocturnal oxygenation, which have wide-ranging consequences on health. Beyond its well-established links to cardiovascular, neurocognitive, and metabolic diseases, recent evidence suggests a possible association between OSA and cancer, particularly lung cancer, one of the leading causes of death worldwide. The advent of immunotherapy has significantly improved outcomes for lung cancer patients in both early and advanced stages. However, immunotherapy is frequently associated with endocrine toxicities, which may overlap or interact with the metabolic alterations observed in OSA. This perspective aims to emphasize the clinical relevance of diagnosing and treating OSA in lung cancer patients undergoing immunotherapy, as proper management could help optimize both therapeutic efficacy and overall health.

## Linked entities

- **Diseases:** obstructive sleep apnea (MONDO:0007147), lung cancer (MONDO:0005138)

## Full-text entities

- **Genes:** Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, E2F3 (E2F transcription factor 3) [NCBI Gene 1871] {aka E2F-3}, IVL (involucrin) [NCBI Gene 3713], PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, AGER (advanced glycosylation end-product specific receptor) [NCBI Gene 177] {aka RAGE, SCARJ1, sRAGE}, PSPC1 (paraspeckle component 1) [NCBI Gene 55269] {aka PSP1}, MIP (major intrinsic protein of lens fiber) [NCBI Gene 4284] {aka AQP0, CTRCT15, LIM1, MIP26, MP26}, TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, EGF (epidermal growth factor) [NCBI Gene 1950] {aka HOMG4, URG}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, HGF (hepatocyte growth factor) [NCBI Gene 3082] {aka DFNB39, F-TCF, HGFB, HPTA, SF}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, TWIST1 (twist family bHLH transcription factor 1) [NCBI Gene 7291] {aka ACS3, BPES2, BPES3, CRS, CRS1, CSO}, APCS (amyloid P component, serum) [NCBI Gene 325] {aka HEL-S-92n, PTX2, SAP}, Cd274 (CD274 antigen) [NCBI Gene 60533] {aka A530045L16Rik, B7h1, Pdcd1l1, Pdcd1lg1, Pdl1}, MDK (midkine) [NCBI Gene 4192] {aka ARAP, MK, NEGF2}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, SLC44A4 (solute carrier family 44 member 4) [NCBI Gene 80736] {aka C6orf29, CTL4, DFNA72, NG22, TPPT, hTPPT1}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, POMC (proopiomelanocortin) [NCBI Gene 5443] {aka ACTH, CLIP, LPH, MSH, NPP, OBAIRH}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, EPCAM (epithelial cell adhesion molecule) [NCBI Gene 4072] {aka Ber-Ep4, BerEp4, DIAR5, EGP-2, EGP314, EGP40}
- **Diseases:** metabolic syndrome (MESH:D024821), melanoma (MESH:D008545), inflammation (MESH:D007249), neurodegenerative diseases (MESH:D019636), rash (MESH:D012871), tumor growth factor (MESH:D006130), Parkinson's (MESH:D010300), cardiac, metabolic, and respiratory diseases (MESH:D012140), hypophysitis (MESH:D000072659), Sleep disorders (MESH:D012893), Tumor (MESH:D009369), endothelial dysfunction (MESH:D014652), diabetes (MESH:D003920), LC (MESH:D008175), gland insufficiency or failure (MESH:D051437), Alzheimer's (MESH:D000544), neurological and cognitive impairments (MESH:D060825), sleep disruption (MESH:D019958), hypoxic (MESH:D002534), lung adenocarcinoma (MESH:D000077192), obesity (MESH:D009765), autoimmune diseases (MESH:D001327), carcinogenesis (MESH:D063646), pneumonitis (MESH:D011014), stroke (MESH:D020521), myocarditis (MESH:D009205), myositis (MESH:D009220), COPD (MESH:D029424), liver and kidney cancers (MESH:D007680), Cushing (MESH:D003480), neuroendocrine and immune dysfunctions (MESH:D018358), Thyroid (MESH:D013966), metabolic diseases (MESH:D008659), inflammatory dysregulation (MESH:D021081), IH (MESH:D000860), lung squamous cell carcinoma (MESH:D002294), metastasis (MESH:D009362), collapse of the upper airway (MESH:D001261), acromegaly (MESH:D000172), hypothyroidism (MESH:D007037), pharyngeal neuropathy (MESH:D010612), death (MESH:D003643), endocrine (MESH:D004700), colitis (MESH:D003092), cardiovascular, neurocognitive, and metabolic diseases (MESH:D002318), insulin resistance (MESH:D007333), craniofacial abnormalities (MESH:D019465), rheumatological toxicities (MESH:D064420), impairment of hormone (MESH:C565870), damage on kidney and heart (MESH:D007674), colorectal and breast cancer (MESH:D001943), heart failure (MESH:D006333), thyroid damage (MESH:D013959), OSA (MESH:D020181), sleep fragmentation (MESH:D012892), type 2 diabetes (MESH:D003924), diabetic ketoacidosis (MESH:D016883), primary hyperaldosteronism (MESH:D006929), interstitial lung diseases (MESH:D017563), hepatitis (MESH:D056486)
- **Chemicals:** oxygen (MESH:D010100), BioRender (-), alcohol (MESH:D000438), ROS (MESH:D017382)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12929550/full.md

## References

130 references — full list in the complete paper: https://tomesphere.com/paper/PMC12929550/full.md

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Source: https://tomesphere.com/paper/PMC12929550