Immunosenescence, inflammaging, and cancer immunotherapy efficacy

Rodriguez, J.E.; Naigeon, Marie; Goldschmidt, Vincent; Dugage, Matthieu Roulleaux; Seknazi, Lauren; Danlos, F-X.; Champiat, Stéphane; Marabelle, Aurélien; Michot, Jean‐Marie; Massard, Christophe; Besse, Benjamin; Ferrara, Roberto; Chaput, Nathalie; Baldini, Capucine

doi:10.1080/14737140.2022.2098718

Cited by 20 publications

(10 citation statements)

References 89 publications

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“…IL1RL1 is a marker of type 2 T-helper cells (Th2), which take an active part in inflammatory reactions in tumors [52,53]. Therefore, it is possible to conclude about participation of the PDL1 c isoform in these processes, considering that inflammatory processes are activated with age, having the name inflammaging [54].…”

Section: Resultsmentioning

confidence: 99%

Expresion paterns of various PDCD1 and PDL1 isoforms in prostate tumors

et al. 2022

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To assess the relative expression (RE) levels of various isoforms of the PDCD1 and PDL1 immune checkpoint genes in prostate tumors, to find the clinically significant alterations in tumors and the correlations with the prostate cancer related and other immune associated genes. Methods. Using quantitative PCR, RE levels of different isoforms of PDCD1 and PDL1 were analyzed in 35 samples of prostate cancer tissues of a different Gleason score (GS) and at various grades, the paired conventionally normal prostate tissue (CNT) samples and 20 prostate adenomas. Results. We have assessed RE levels for 5 variants of long and short isoforms of PDCD1 and PDL1 in prostate cancer and noncancerous tissue samples. We detected a significant decrease of RE levels of PDL1 long isoforms in prostate cancer with GS>7, compared with the adenoma group. Noteworthy, RE of short isoforms of PDCD1 and PDL1 has positive correlations with the age. The RE patterns of PDCD1 and PDL1 isoforms demonstrated significant correlations with the expression of 31 genes, related to tumor-associated macrophages, fibroblasts and immune cell markers in the prostate cancer group. Conclusions. The studied genes are involved in the prostate cancer progression, related to inflammation. The RE levels showed high dispersion in all groups of prostate tissue samples. We propose to assess the RE levels of the PDCD1 and PDL1 genes long isoforms, before prescribing immunotherapy methods, to analyse the putative sensitivity of tumors to such treatment. Further studies are needed to confirm the presented here results on a larger patient cohort. K e y w o r d s: prostate tumors, relative gene expression, PDCD1, PDL1, long and short isoforms, pharmacological markers.

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Section: Resultsmentioning

confidence: 99%

Expresion paterns of various PDCD1 and PDL1 isoforms in prostate tumors

et al. 2022

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“…Systemic inflammation is known to induce both CMV reactivation ( 41 ) and immunosenescence, with a major role of the SASP in promoting and maintaining immune aging ( 8 ). Unexpectedly, plasmatic IL-8 was decreased in T 8 sen high patients.…”

Section: Discussionmentioning

confidence: 99%

“…Aging is associated with several structural and functional changes in the immune system, which are classified under the term “immunosenescence,” affecting both innate and adaptive response. Along with the persistence of proinflammatory stimuli, immunosenescence is also associated with a senescent-associated secretory phenotype (SASP) of immune cells ( 7 ), which contributes to “inflammaging,” i.e., a low level of systemic inflammation with higher levels of interleukin-6 (IL-6), IL-8, and C-reactive protein ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Human virome profiling identified CMV as the major viral driver of a high accumulation of senescent CD8 ⁺ T cells in patients with advanced NSCLC

Naigeon,

Roulleaux Dugage,

Danlos

et al. 2023

Sci. Adv.

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Circulating senescent CD8 + T (T 8 sen) cells are characterized by a lack of proliferative capacities but retain cytotoxic activity and have been associated to resistance to immunotherapy in patients with advanced non–small cell lung cancer (aNSCLC). We aimed to better characterize T 8 sen and to determine which factors were associated with their accumulation in patients with aNSCLC. Circulating T 8 sen cells were characterized by a higher expression of SA-βgal and the transcription factor T-bet, confirming their senescent status. Using whole virome profiling, cytomegalovirus (CMV) was the only virus associated with T 8 sen. CMV was necessary but not sufficient to explain high accumulation of T 8 sen (T 8 sen high status). In CMV + patients, the proportion of T 8 sen cells increased with cancer progression. Last, CMV-induced T 8 sen high phenotype but not CMV seropositivity itself was associated with worse progression-free and overall survival in patients treated with anti–PD-(L)1 therapy but not with chemotherapy. Overall, CMV is the unique viral driver of T 8 sen-driven resistance to anti–PD-(L)1 antibodies in patients with aNSCLC.

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“…These include a reduction in bone marrow functions; a decrease in the size of other organs, such as the thymus, lymph nodes, and spleen; a reduction in the antigenic diversity of immune cells; a decrease in the co-stimulatory molecule expression on T lymphocytes; and a reduction in the antibody production of B lymphocytes. Moreover, “inflammaging”, a low-grade chronic inflammation state, is frequent with advanced age, and it is related to an increase in pro-inflammatory cytokines [ 36 , 37 ]. Conversely, Erbe and colleagues found biomarkers within a multi-omics database that were associated with an ICI response (such as TMB, ICI-related gene expression in selected tumors, and a more immune-stimulatory signaling TME) and were particularly enriched in tumors from older patients compared to those of their younger counterparts [ 38 ].…”

Section: Io In Elderly Nsclc Patientsmentioning

confidence: 99%

Immune Checkpoint Inhibitors in “Special” NSCLC Populations: A Viable Approach?

Bronte

Cosi

Magri

et al. 2023

IJMS

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Over the last decade, the therapeutic scenario for advanced non-small-cell lung cancer (NSCLC) has undergone a major paradigm shift. Immune checkpoint inhibitors (ICIs) have shown a meaningful clinical and survival improvement in different settings of the disease. However, the real benefit of this therapeutic approach remains controversial in selected NSCLC subsets, such as those of the elderly with active brain metastases or oncogene-addicted mutations. This is mainly due to the exclusion or underrepresentation of these patient subpopulations in most pivotal phase III studies; this precludes the generalization of ICI efficacy in this context. Moreover, no predictive biomarkers of ICI response exist that can help with patient selection for this therapeutic approach. Here, we critically summarize the current state of ICI efficacy in the most common “special” NSCLC subpopulations.

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Immunosenescence, inflammaging, and cancer immunotherapy efficacy

Cited by 20 publications

References 89 publications

Expresion paterns of various PDCD1 and PDL1 isoforms in prostate tumors

Expresion paterns of various PDCD1 and PDL1 isoforms in prostate tumors

Human virome profiling identified CMV as the major viral driver of a high accumulation of senescent CD8 ⁺ T cells in patients with advanced NSCLC

Immune Checkpoint Inhibitors in “Special” NSCLC Populations: A Viable Approach?

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Immunosenescence, inflammaging, and cancer immunotherapy efficacy

Cited by 20 publications

References 89 publications

Expresion paterns of various PDCD1 and PDL1 isoforms in prostate tumors

Expresion paterns of various PDCD1 and PDL1 isoforms in prostate tumors

Human virome profiling identified CMV as the major viral driver of a high accumulation of senescent CD8 + T cells in patients with advanced NSCLC

Immune Checkpoint Inhibitors in “Special” NSCLC Populations: A Viable Approach?

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Human virome profiling identified CMV as the major viral driver of a high accumulation of senescent CD8 ⁺ T cells in patients with advanced NSCLC