The Effectiveness of Cancer Immune Checkpoint Inhibitor Retreatment and Rechallenge—A Systematic Review

Perdyan, Adrian; Sobocki, Bartosz Kamil; Balihodzic, Amar; Dąbrowska, Anna; Kacperczyk, Justyna; Rutkowski, Jacek

doi:10.3390/cancers15133490

Cited by 8 publications

(4 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Likewise, will the patients with aCC whose tumors progress on or after prior anti-PD-1 ICI benefit from PD-L1 inhibition in a subsequent line, or vice versa? To our knowledge, there is no proof-of-concept prospective trial for anti-PD(L)1 ICI re-treatment or rechallenge upon relapse or PD, respectively, in solid tumor oncology although retrospective experiences for other cancer types suggest feasibility of this approach, with greater clinical benefit in patients who derived disease control from a preceding course of ICI and less so in those who received intervening treatment(s) between 2 ICI courses [ 38 39 40 ]. These are questions which are best clarified by well-designed clinical trials, ideally with preplanned biospecimen collection for translational research.…”

Section: Future Directionsmentioning

confidence: 99%

Evolving standards and future directions for systemic therapies in cervical cancer

Ang,

Chan

2024

J Gynecol Oncol

View full text Add to dashboard Cite

Several groundbreaking clinical trials with the potential to transform the management paradigm of both locally advanced and persistent, recurrent, or metastatic cervical cancers have been presented in 2023. This review describes the reported data from INTERLACE and KEYNOTE-A18 in the locally advanced setting, as well as BEATcc, innovaTV 301 and DESTINY-PanTumor02 for advanced disease. The practice implications of their positive results are interpreted in the context of global health considerations, and updated treatment algorithms are proposed. Furthermore, emerging trends in drug development for cervical cancer are discussed. As the routine use of immune checkpoint inhibitors (ICIs) for curative and palliative indications increases in the foreseeable future, patients whose cervical cancers which persist, relapse or progress after prior ICI exposure will represent an area of unmet clinical need and form the key target population for next-generation trials. Future research will help shape oncologists’ approaches in the optimal selection, sequencing and re-treatment or rechallenge of immuno-oncology agents and/or antibody-drug conjugates in women with cervical cancer.

show abstract

Section: Future Directionsmentioning

confidence: 99%

Evolving standards and future directions for systemic therapies in cervical cancer

Ang,

Chan

2024

J Gynecol Oncol

View full text Add to dashboard Cite

show abstract

“…The capacity of non-metastatic tdLNs to act as an ongoing source of TCF-1+ TSL, as recently reported 7-9 , could become dysregulated by PD-1 checkpoint immunotherapy, leading to impaired long-term maintenance of high affinity TSL clones in the tdLNs, the loss of which could be permanent due to reduced naïve T cell output from the adult thymus 60,61 . Recent clinical evidence reporting a declining efficacy of repetitive checkpoint treatment in patients experiencing tumor relapse fits with this view 62 . Finally, our findings indicate that partial blockade of PD-1 pathway could avoid loss of high affinity TSL at the price of decreased anti-tumor efficacy in any single round of treatment, suggesting that a 'sweet spot' could be found through careful titration of checkpoint blockade antibody dosage.…”

Section: Discussionmentioning

confidence: 81%

PD-1 controls differentiation, survival, and TCR affinity evolution of stem-like CD8+ T cells

Hor,

Schrom,

Wong-Rolle

et al. 2024

Preprint

View full text Add to dashboard Cite

Stem-like progenitors are a critical subset of cytotoxic T cells that self-renew and give rise to expanded populations of effector cells critical for successful checkpoint blockade immunotherapy. Emerging evidence suggests that the tumor-draining lymph nodes can support the continuous generation of these stem-like cells that replenish the tumor sites and act as a critical source of expanded effector populations, underlining the importance of understanding what factors promote and maintain activated T cells in the stem-like state. Using advanced 3D multiplex immunofluorescence imaging, here we identified antigen-presentation niches in tumor-draining lymph nodes that support the expansion, maintenance, and affinity evolution of a unique population of TCF-1+PD-1+SLAMF6histem-like CD8+ T cells. Our results show that contrary to the prevailing view that persistent TCR signaling drives terminal effector differentiation, prolonged antigen engagement well beyond the initial priming phase sustained the proliferation and self-renewal of these stem-like T cellsin vivo. The inhibitory PD-1 pathway plays a central role in this process by mediating the fine-tuning of TCR and co-stimulatory signal input that enables selective expansion of high affinity TCR stem-like clones, enabling them to act as a renewable source of high affinity effector cells. PD-1 checkpoint blockade disrupts this fine tuning of input signaling, leading to terminal differentiation to the effector state or death of the most avid anti-tumor stem-like cells. Our results thus reveal an unexpected relationship between TCR ligand affinity recognition, a key negative feedback regulatory loop, and T cell stemness programming. Furthermore, these findings raise questions about whether anti-PD-1 checkpoint blockade during cancer immunotherapy provides a short-term anti-tumor effect that comes at the cost of diminishing efficacy due to progressive loss of these critical high affinity stem-like precursors.

show abstract

“…Lastly, immunotherapy to treat cancer has gained some successes and stimulated new excitement in recent years (Ribas and Wolchok, 2018;Esfahani et al, 2020;Perdyan et al, 2023). The new developments enable the engineering of immune cells targeting specific cancer antigens, and also provide strategies to active the immune system by blocking the ability of cancer cells to evade immune cells.…”

Section: Cancer Treatment/therapymentioning

confidence: 99%

Cell death in cancer chemotherapy using taxanes

Xu,

Smith

et al. 2024

Front. Pharmacol.

View full text Add to dashboard Cite

Cancer cells evolve to be refractory to the intrinsic programmed cell death mechanisms, which ensure cellular tissue homeostasis in physiological conditions. Chemotherapy using cytotoxic drugs seeks to eliminate cancer cells but spare non-cancerous host cells by exploring a likely subtle difference between malignant and benign cells. Presumably, chemotherapy agents achieve efficacy by triggering programmed cell death machineries in cancer cells. Currently, many major solid tumors are treated with chemotherapy composed of a combination of platinum agents and taxanes. Platinum agents, largely cis-platin, carboplatin, and oxaliplatin, are DNA damaging agents that covalently form DNA addicts, triggering DNA repair response pathways. Taxanes, including paclitaxel, docetaxel, and cabazitaxel, are microtubule stabilizing drugs which are often very effective in purging cancer cells in clinical settings. Generally, it is thought that the stabilization of microtubules by taxanes leads to mitotic arrest, mitotic catastrophe, and the triggering of apoptotic programmed cell death. However, the precise mechanism(s) of how mitotic arrest and catastrophe activate the caspase pathway has not been established. Here, we briefly review literature on the involvement of potential cell death mechanisms in cancer therapy. These include the classical caspase-mediated apoptotic programmed cell death, necroptosis mediated by MLKL, and pore forming mechanisms in immune cells, etc. In particular, we discuss a newly recognized mechanism of cell death in taxane-treatment of cancer cells that involves micronucleation and the irreversible rupture of the nuclear membrane. Since cancer cells are commonly retarded in responding to programmed cell death signaling, stabilized microtubule bundle-induced micronucleation and nuclear membrane rupture, rather than triggering apoptosis, may be a key mechanism accounting for the success of taxanes as anti-cancer agents.

show abstract

The Effectiveness of Cancer Immune Checkpoint Inhibitor Retreatment and Rechallenge—A Systematic Review

Cited by 8 publications

References 68 publications

Evolving standards and future directions for systemic therapies in cervical cancer

Evolving standards and future directions for systemic therapies in cervical cancer

PD-1 controls differentiation, survival, and TCR affinity evolution of stem-like CD8+ T cells

Cell death in cancer chemotherapy using taxanes

Contact Info

Product

Resources

About