The Combination of Radiotherapy With Immunotherapy and Potential Predictive Biomarkers for Treatment of Non-Small Cell Lung Cancer Patients

Meng, Lei; Xu, Jianfang; Ye, Ying; Wang, Yingying; Luo, S.; Gong, Xuejun

doi:10.3389/fimmu.2021.723609

Cited by 24 publications

(17 citation statements)

References 156 publications

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“…A limitation of this study is our focus on NSCLC patients who received a single therapy, which is no longer the standard of care ( 45 , 63 , 64 ). However, as anti-PD-1 is well utilized in combination therapy, finding markers that dictate positive responses to anti-PD-1 remains highly useful.…”

Section: Discussionmentioning

confidence: 99%

CD33 Expression on Peripheral Blood Monocytes Predicts Efficacy of Anti-PD-1 Immunotherapy Against Non-Small Cell Lung Cancer

et al. 2022

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Non-small cell lung carcinoma (NSCLC) is the leading cause of cancer-related deaths globally. Immune checkpoint blockade (ICB) has transformed cancer medicine, with anti-programmed cell death protein 1 (anti-PD-1) therapy now well-utilized for treating NSCLC. Still, not all patients with NSCLC respond positively to anti-PD-1 therapy, and some patients acquire resistance to treatment. There remains an urgent need to find markers predictive of anti-PD-1 responsiveness. To this end, we performed mass cytometry on peripheral blood mononuclear cells from 26 patients with NSCLC during anti-PD-1 treatment. Patients who responded to anti-PD-1 ICB displayed significantly higher levels of antigen-presenting myeloid cells, including CD9+ nonclassical monocytes, and CD33hi classical monocytes. Using matched pre-post treatment samples, we found that the baseline pre-treatment frequencies of CD33hi monocytes predicted patient responsiveness to anti-PD-1 therapy. Moreover, some of these classical and nonclassical monocyte subsets were associated with reduced immunosuppression by T regulatory (CD4+FOXP3+CD25+) cells in the same patients. Our use of machine learning corroborated the association of specific monocyte markers with responsiveness to ICB. Our work provides a high-dimensional profile of monocytes in NSCLC and links CD33 expression on monocytes with anti-PD-1 effectiveness in patients with NSCLC.

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Section: Discussionmentioning

confidence: 99%

CD33 Expression on Peripheral Blood Monocytes Predicts Efficacy of Anti-PD-1 Immunotherapy Against Non-Small Cell Lung Cancer

et al. 2022

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“…Current candidate biomarkers also include ( 76 ) (1): Cell surface markers: FAS ligands and tumor antigen-specific T cells. (2) Tumor infiltrating lymphocytes (TIL): CD8 + TIL, PD-1 + CD8 + T cells, PD-L1 high regulatory T cells (Tregs).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of radiotherapy/chemoradiotherapy combined with immune checkpoint inhibitors for locally advanced stages of esophageal cancer: A systematic review and meta-analysis

Deng

et al. 2022

Front. Oncol.

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BackgroundRadiotherapy (RT)/Chemoradiotherapy (CRT) are important treatments for all stages of esophageal cancer (EC). The combination of immune checkpoint inhibitors (ICIs) with RT/CRT seems to be promising avenue for the treatment of EC. Therefore, a systematic review and meta-analysis was performed in order to assess the safety and efficacy of RT/CRT and ICI combination therapy for EC patients.MethodsPubMed and several other databases were searched (according to specific criteria) to find relevant studies published prior to the 31st of December 2021.Results1962 articles were identified for screening, and six trials containing 668 patients were identified and pooled to determine the one- and two-year overall survival (OS), which were 84.5% (95% confidence interval (CI): 69.9%-100%) and 68.3% (95% CI: 49.0%-95.1%), respectively. Additionally, the rate of pooled grade 3-5 adverse reactions was 41.0% (95% CI: 31.2%-51.2%). The rate of specific grade 3-5 adverse reactions are as follows: lymphopenia (36.8%-60%), esophagitis (20%), anastomotic leakage (18%), esophageal fistula (10%), pain (10%), leukopenia (5.3%-10%), esophageal hemorrhage (2.5%-5%), chyle leakage (3%), fatigue (5%), cough (2.7%-5%), diarrhea (2.7%), pulmonary embolism (2.5%) and allergic reaction (2.5%). The pooled rate of pneumonitis of grade 3-5 and grade 1-5 was 0.8% (95% CI: 0.1%-0.16%, I2: 0%) and 5.4% (95% CI: 2.0%-14.2%, I2: 82%). For thoracic complication, esophagitis was 63.6% (95% CI: 42.4%-80.6%), which appeared to be more frequent with the combination of ICIs to RT/CRT (12%-37.7%). Other thoracic complications include esophageal hemorrhage (2.5%-10%), esophageal fistula (6%-10%) and anastomotic leakage (6%-21%). Additionally, some of the trials did not report cardiac related adverse reactions. The subgroup analyses also revealed that the pooled rate patients with grade 3-5 pneumonitis was higher for CRT/RT with concurrent and sequential ICI treatment (1.9%) than other groups (0.8%).ConclusionThis study suggests that the addition of ICIs to RT/CRT for EC patients may be both safe and feasible. However, larger randomized studies are needed to confirm these results.

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“…Therefore, nab-paclitaxel might be a good combination drug with immunotherapy. Additionally, radiotherapy could positively modulate thelandscape of the immune microenvironment and systemic response and enhance the anticancer activity of immunotherapy ( 30 ). For this patient, the sequential treatment with radiotherapy and pembrolizumab successfully repressed the progression of retroperitoneal lymph node metastases.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Successful Immunotherapy Improved the Prognosis of the Unfavorable Subset of Cancer of Unknown Primary

et al. 2022

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BackgroundCancer of unknown primary (CUP) is heterogeneous and has a wide variety of clinical presentations and a poor prognosis in most patients, with a median overall survival of only 6 months. The development of molecular profiling contributes to precision therapy, and targeted drugs and immune checkpoint inhibitors (ICIs) greatly promote individualized treatment.Case presentationHere, we reported a case of an unfavorable subset of CUP who had a long time of survival after the immunotherapy-prominent comprehensive treatment. A 48-year-old man presented with back pain and a cough. A diagnostic work-up showed bone marrow, multiple bones, and lymph node metastasis. Lymph node pathology implies metastatic poorly differentiated cancer. Next-generation sequencing (NGS) showed no special targets, but the tumor proportion score (TPS) of programmed death-ligand 1 (PD-L1) was 80% and the tumor mutation burden (TMB) was 16.7 per million bases. After two cycles of pembrolizumab 200 mg D1 plus nanoparticle albumin-bound (nab)-paclitaxel 200 mg D1&8 (q3w), PET-CT and bone marrow aspiration cytology showed a complete response (CR). Subsequently, pembrolizumab alone was used for three months. The left inguinal lymph nodes showed new metastasis. After two cycles of the combination treatment of pembrolizumab and (nab)-paclitaxel, a partial response (PR) was achieved. After seven months, retroperitoneal lymph nodes showed new metastasis, and the sequential treatment with radiotherapy and pembrolizumab exhibited encouraging efficacy. To date, the patient has survived nearly 40 months with the combination therapy.ConclusionsThe ICI-prominent comprehensive treatment provided clinical benefit for the reported case of CUP. Thus, CUP patients with markers of benefiting from immunotherapy should be actively treated with immunotherapy to improve their prognosis.

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The Combination of Radiotherapy With Immunotherapy and Potential Predictive Biomarkers for Treatment of Non-Small Cell Lung Cancer Patients

Cited by 24 publications

References 156 publications

CD33 Expression on Peripheral Blood Monocytes Predicts Efficacy of Anti-PD-1 Immunotherapy Against Non-Small Cell Lung Cancer

CD33 Expression on Peripheral Blood Monocytes Predicts Efficacy of Anti-PD-1 Immunotherapy Against Non-Small Cell Lung Cancer

Efficacy and safety of radiotherapy/chemoradiotherapy combined with immune checkpoint inhibitors for locally advanced stages of esophageal cancer: A systematic review and meta-analysis

Case Report: Successful Immunotherapy Improved the Prognosis of the Unfavorable Subset of Cancer of Unknown Primary

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