Cervical microbiota composition is associated with cervical HPV infection and CIN severity. Previous studies only assessed the total association between cervical microbiota and HPV infections or CINs, and yet no study reported the direct and indirect associations between cervical microbiota and CINs mediated by HPV infection, respectively. The aim of this study was to investigate the direct and indirect associations between microbiotas and CIN severity. Cervical microbiota of 126 women with CIN 1− (normal cytology and CIN 1) and 40 with CIN 2+ (CIN 2 and CIN 3) were analyzed using Illumina sequencing based on the 16S rRNA gene. HPV was detected using a highly sensitive PCR primer set (SPF1/GP6+). Indirect effects of Pseudomonas stutzeri, Bacteroides fragilis, Lactobacillus delbrueckii, Atopobium vaginae, and Streptococcus agalactiae mediated by HPV infection on CIN status were observed. The directions of the direct and the indirect associations between CIN status and Ps. stutzeri were opposite. The directions of the direct and the indirect associations between CIN status and A. vaginae were the same. B. fragilis, L. delbrueckii, and S. agalactiae only had indirect association with CIN status. In summary, our study provided suggestive evidence that some microbial populations could have direct or indirect effects mediated by affecting HPV infection on CIN progression. Besides HPV infection, microbial community composition possibly plays a role in cervical carcinogenesis.

Background: The functional role of lung microbiota has attracted an accumulating attention recently, but the profile and functional role of the lung microbiota in patients with lung cancer remained largely unknown. Methods: To evaluate the association of the microbiota with lung cancer, we performed comparative analysis of the lung microbiota using 16S rRNA amplicon sequencing approach in the paired bronchoalveolar lavage fluid (BALF) samples (paired samples from cancerous lung and the contralateral non-cancerous lung) from 50 cancer patients with unilateral lobar masses. Results: We found that the relative abundance of phylum Tenericutes, its class Mollicutes, its order Entomoplasmatales, its family Spiroplasmataceae, and its genus Spiroplasma was significantly increased in cancerous lung, but the relative abundance of phylum Bacteroidetes, its class Bacteroidia, and its order Bacteroidales was significantly decreased in cancerous lung. In addition, the relative abundance of family Leuconostocaceae and its genus Weissella was significantly increased in cancerous lung. Conclusion: Our findings provide insights into a change of lung microbiota community associated with the development of lung cancer.

Background T cell receptor-engineered T cells (TCR-Ts) therapy is a promising cancer treatment strategy. Nowadays, most studies focused on identification of high-avidity T cell receptors (TCRs) directed against neoantigens derived from somatic mutations. However, few neoantigens per patient could induce immune response in epithelial cancer and additionally many tumor-specific antigens could be derived from noncoding region. Autologous tumor cells (ATCs) could be unbiased stimulators in activating and enriching tumor-reactive T cells. However, it’s unknown if T cells engineered to express TCRs isolated from tumor-reactive T cells enriched by ATCs have strong antitumor response. Methods In this study, multiple TIL fragments obtained from a patient with esophageal squamous cell carcinoma (ESCC) were screened for specific recognition of ATCs. Tumor-reactive TILs were enriched by in vitro repeated stimulation of ATCs and isolated based on CD137 upregulation. Subsequently, tumor-reactive TCR was obtained by single-cell RT-PCR analysis and was introduced into peripheral blood lymphocytes to generate TCR-Ts. Results We found that phenotype and effect function of TIL fragments derived from different tumor sites were spatially heterogeneous. Of four TIL fragments, only TIL-F1 could specifically identify ATCs. Subsequently, we isolated CD8⁺ CD137⁺ T cells from pre- and post-stimulated TIL-F1 co-cultured with ATCs, and identified their most dominant TCR. This TCR was introduced into PBLs to generate TCR-Ts, which specifically identified and killed ATCs in vivo and in vitro. Conclusion This strategy provides the means to generate tumor-reactive TCR-Ts for ESCC, which is especially important for patients without prior knowledge of specific epitopes and might be applied for other cancers.

To explore whether a few nonsynonymous somatic mutations could induce activation and proliferation of neoantigen‐specific tumour‐infiltrating lymphocytes (TILs) in tumours with low mutation rates, we analysed a patient with multifocal papillary thyroid carcinoma (seven noncontiguous cancer foci) to investigate the relationship between neoantigens and TILs. These seven foci had a few or no nonsynonymous somatic mutations; moreover, multiple loci had similar or different spectra of mutations. We used high‐throughput sequencing of the rearranged genes in T cell receptor β‐chain (TCRβ) to reveal the basic characteristics of T cells in seven tumour foci and matched adjacent normal tissue. We found that in multifocal papillary thyroid carcinoma the number of nonsynonymous somatic mutations was positively associated with oligoclonal TCRβ repertoire, and tumour foci with similar spectra of mutations had higher overlap of TCRβ repertoire. In conclusion, the number of nonsynonymous somatic mutations is small in tumours with low mutation rates but these mutations still play an important role in activating neoantigen‐specific TILs.