Table 3.

Immune recovery post-cancer treatment for solid tumours stratified by cancer treatment class

Cancer treatment class	Expert opinion
Chemotherapy	Patients receiving chemotherapy will experience varying degrees of short-term impaired immunity depending on the chemotherapy regimen used, the extent of systemic corticosteroid support required, and baseline patient characteristicsa. Proliferating hematopoietic stem and progenitor cells (HSPCs) in the bone marrow are particularly susceptible to chemotherapy-induced damage [126] White blood cell count nadirs depend on the antineoplastic therapy used and typically occur around 10–14 days after administration of treatment, with complete recovery by day 21–28 [127]b
Immune checkpoint inhibitor therapies (e.g. CTLA4 or PD1-PDL1 inhibitors)	Do not usually cause immune deficitsc. In contrast, they are designed to stimulate immune function by blocking inhibitory checkpoints, such as CTLA4 and PD1-PDL1. The extended duration of the therapeutic effects of ICIs (and their auto-immune toxicities) often far surpasses their pharmacokinetic half-life and is highly variable [128, 129]
Radiation therapy	Advances in radiation for the treatment of solid tumours have led to improved tumour targeting with reduced impact on normal tissues. Immune deficits are uncommon post-treatment [130]d
Endocrine and targeted therapies (e.g. kinase or VEGF-targeting angiogenesis inhibitors)	Most of these therapies are not expected to have significant effects on immune deficits and/or immune reconstitution. Some kinase inhibitors can cause neutropenia and are taken daily for years [131, 132]

CTLA4 cytotoxic T-lymphocyte-associated antigen 4, ICI Immune checkpoint inhibitor, PD1 programmed cell death 1, PDL1 programmed cell death ligand 1, VEGF vascular endothelial growth factor

^aIn the setting of non-curative/palliative chemotherapy, patients may have some permanent immune suppression related to the chronic malignancy itself, receipt of multiple lines of chemotherapy, and long-term palliative use of corticosteroids, with cumulative effects on neutrophils and neutrophil recovery (more suppression, longer time to recovery, and sometimes long-lasting modest neutropenia). Further, patients may have had palliative radiation therapy, and if a larger extent of their marrow is in the radiation field, the myelosuppression/neutropenia from chemotherapy may be more severe and long lasting [133]

^bSome reports indicate that it could take up to 1 year for cluster of differentiation 4 (CD4)⁺ T cells to recover. The repopulating cells have a reduced proportion of naïve cells and an increased memory component, however clinical significance to our topic is not known [134]

^cSome patients with ICI require immunosuppressive therapy with long-term corticosteroids or mycophenolate to treat immune-related adverse effects [128]

^dShould more than one-third of skeletal marrow reserve be radiated (mostly spine, pelvis, and sternum), long-lasting cytopenia may occur. Moreover, radiation-suppressed marrow reserve may result in greater susceptibility to severe myelosuppression with chemotherapy [133]. At higher doses of radiation, immune suppression occurs, while lower levels of radiation have subtle but persistent immune function alterations that can be immunosuppressive or immunostimulatory [135–137]. In a small series of irradiated Stage I–III patients with breast cancer, decreased TNF and lymphocyte counts persisted after ionising radiation [138]