Lung cancer (LC) is the leading cause of cancer-related death worldwide due to its late diagnosis and poor outcomes. As has been found for other types of tumors, there is increasing evidence that myeloid-derived suppressor cells (MDSCs) play important roles in the promotion and progression of LC. Here, we briefly introduce the definition of MDSCs and their immunosuppressive functions. We next specifically discuss the multiple roles of MDSCs in the lung tumor microenvironment, including those in tumor growth and progression mediated by inhibiting antitumor immunity, and the associations of MDSCs with a poor prognosis and increased resistance to chemotherapy and immunotherapy. Finally, we also discuss preclinical and clinical treatment strategies targeting MDSCs, which may have the potential to enhance the efficacy of immunotherapy.

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Myeloid-derived suppressor cells-new and exciting players in lung cancer

Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation

Natural killer (NK) cells play a critical role in the antitumor immunity. Ionizing radiation (IR) has a pronounced effect on modifying NK cell biology, while the molecular mechanisms remain elusive. In this review, we briefly introduce the anti-tumor activity of NK cells and summarize the impact of IR on NK cells both directly and indirectly. On one hand, low-dose ionizing radiation (LDIR) activates NK functions while high-dose ionizing radiation (HDIR) is likely to partially impair NK functions, which can be reversed by interleukin (IL)-2 pretreatment. On the other hand, NK functions may be adjusted by other immune cells and the alternated malignant cell immunogenicity under the settings of IR. Various immune cells, such as the tumor-associated macrophage (TAM), dendritic cell (DC), regulatory T cell (Treg), myeloid-derived suppressor cell (MDSC), and tumor exhibited ligands, such as the natural killer group 2 member D ligand (NKG2DL), natural cytotoxicity receptors (NCR) ligand, TNF-related apoptosis-inducing ligand-receptor (TRAIL-R), and FAS, have been involved in this process. Better understanding the molecular basis is a promising way in which to augment NK-cell-based antitumor immunity in combination with IR.

/pdf/immunomodulation-of-nk-cells-by-ionizing-radiation-ev0xaa2hx8.pdf

Immunomodulation of NK Cells by Ionizing Radiation.

Anti-angiogenic agents in the age of resistance to immune checkpoint inhibitors: Do they have a role in non-oncogene-addicted non-small cell lung cancer?

MDSCs, ageing and inflammageing

An immunophenotyping analysis was performed in peripheral blood samples from seven patients with lung cancer unfit for surgery treated with stereotactic body radiotherapy (SBRT). The objective was to characterize the effect of SBRT on the host immune system. Four patients received 60 Gy (7.5 Gy × 8) and three 50 Gy (12.5 Gy × 4). Analyses were performed before SBRT, 72 h after SBRT, and at one, three, and six months after the end of SBRT. Of note, there was a specific increase of the immunoactive component of the immune system, with elevation of CD56+highCD16+ natural killer (NK) cells (0.95% at baseline to 1.38% at six months), and a decrease of the immunosuppressive component of the immune system, with decreases of CD4+CD25+Foxp3+CDA5RA− regulatory T cells (4.97% at baseline to 4.46% at six months), granulocytic myeloid-derived suppressor cells (G-MDSCs) (from 66.1% at baseline to 62.6% at six months) and monocytic (Mo-MDSCs) (8.2% at baseline to 6.2% at six months). These changes were already apparent at 72 h and persisted over six months. SBRT showed an effect on systemic immune cell populations, which is a relevant finding for supporting future combinations of SBRT with immunotherapy for treating lung cancer patients.

/pdf/preliminary-study-of-the-effect-of-stereotactic-body-14sjegt9mn.pdf

Preliminary Study of the Effect of Stereotactic Body Radiotherapy (SBRT) on the Immune System in Lung Cancer Patients Unfit for Surgery: Immunophenotyping Analysis.

418P Colorectal cancer lung metastases resection and its impact on survival in the oligometastatic setting

Introduction and aim A1AT deficiency has been related to the early onset of emphysema, this is considered a risk for LC. The objective of this study is to determine the presence of HA1AT mutations, their association with A1AT serum levels, and the presence of LC in patients with COPD. Methods: A cross-sectional and analytical study was carried out&nbsp;on 120 COPD patients, classified into two groups: COPD with cancer (n=39) and COPD without cancer (n=81). A buccal smear was collected for the genetic study of 14 mutations using Alphakit, Progenika Biopharma. Clinical, analytical, and functional variables were collected. Results: In the study population, 82 (68%) patients were male with a median age of 60 years [55.5-64]. Patients with COPD and cancer were older (64 [58-75] vs. 59 [55-62]; p&lt;0.001) and had better lung function and less emphysema (28 patients vs 70 patients). They also had a significant increase in inflammatory parameters (Neutrophil-lymphocyte ratio, p&lt;0.001;&nbsp;Platelet-lymphocyte ratio, p&lt;0.001; and A1AT levels, p&lt;0.001). HA1AT mutations were detected in 21 patients (26%) of the COPD group without cancer and 5 mutations in the cancer group, being the M/S the most prevalent mutation (n=18). In multivariate analysis, the presence of the mutation was associated with lower serum A1AT levels (p = 0.003). However, LC had a positive association with A1AT serum levels (p = 0.001). Conclusions: The presence of HA1AT mutations wasn’t related to the diagnosis of LC. Heterozygous mutations were associated with lower serum A1AT levels. Lung cancer patients presented higher protein levels of A1AT, which can be seen as an inflammatory marker.

Susana Padrones Sánchez

Papers

Preliminary Study of the Effect of Stereotactic Body Radiotherapy (SBRT) on the Immune System in Lung Cancer Patients Unfit for Surgery: Immunophenotyping Analysis.

418P Colorectal cancer lung metastases resection and its impact on survival in the oligometastatic setting

Heterozygous alpha 1 antitrypsin mutations (HA1AT) and lung cancer (LC) in a chronic obstructive pulmonary disease (COPD) population.