Immune checkpoint expression on peripheral cytotoxic lymphocytes in cervical cancer patients: moving beyond the PD-1/PD-L1 axis.

Immune checkpoint therapy to reverse natural killer (NK) and T cell exhaustion has emerged as a promising treatment in various cancers. While anti-programmed cell death 1 (PD-1) pembrolizumab has recently gained Food and Drug Administration (FDA) approval for use in recurrent or metastatic cervical cancer, other checkpoint molecules, such as T cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibition motif (ITIM) domains (TIGIT) and T cell immunoglobulin and mucin-domain containing-3 (Tim-3), have yet to be fully explored in this disease. We report expression of TIGIT, Tim-3 and PD-1 on subsets of peripheral blood NK (CD56dim/neg CD16bright/dim/neg and CD56bright CD16dim/neg ) and T cells. The percentages of these cells were increased in women with cervical cancer and pre-malignant lesions. PD-1+ NK and T cells were likely to co-express TIGIT and/or Tim-3. These cells, with an apparently 'exhausted' phenotype, were augmented in patients. A subset of cells were also natural killer group 2 member D (NKG2D)- and DNAX accessory molecule 1 (DNAM-1)-positive. PD-1int and PD-1high T cells were notably increased in cervical cancer. Soluble programmed cell death ligand 1 (PD-L1) was higher in cancer patient blood versus healthy donors and we observed a positive correlation between sPD-L1 and PD-1+ T cells in women with low-grade lesions. Within the cancer group, there were no significant correlations between sPD-L1 levels and cervical cancer stage. However, when comparing cancer versus healthy donors, we observed an inverse association between sPD-L1 and total T cells and a correlation between sPD-L1 and CD56dim NK cells. Our results may show an overview of the immune response towards pre-cancerous lesions and cervical cancer, perhaps giving an early clue as to whom to administer blocking therapies. The increase of multiple checkpoint markers may aid in identifying patients uniquely responsive to combined antibody therapies.

[Lymphatic axillary metastasis in cancer of the breast]. / Metástasis ganglionar axilar del cáncer de mama.

From 1978 at the Gynecology service of the Hospital Civil of Guadalajara we conducted a study with 50 patients with breast cancer in which we related the size tumor with some risk factors of breast cancer with axilar ganglionar metastasis. The average size of the tumor was 4.9 cm, 21 patients (42%) had evidence of ganglionar axilar metastasis, 64% were located in the upper-outer quadrant, the average age was 52.7 years, 52% were pre-menopausic, 20% had backgrounds of bening disease of the breast and 20% had familiar backgrounds of breast cancer. 31.8% of the tumors from 2-4 cm had axillar metastasis vs 52.2% of tumors from the upper-outer quadrant and 80% from the upper-outer and inner quadrant had axillar metastasis. Only in 33.3% of the patients under 40 years old, axillar metastasis was found. The hormonal state, the background of bening disease and familiar backgrounds of breast cancer had no relationship with the incidence of axillar ganglionar metastasis. In conclusion, axillar ganglionar metastasis has a direct relation with the size of the breast tumor and its location.

[Primary invasive carcinoma of the vagina and 3d degree genital prolapse. Presentation of a case]. / Carcinoma primario invasivo de vagina y prolapso genital de tercer grado. Presentación de un caso.

Primary carcinoma invading vagina is a rare entity, and more so, being associated to genital prolapse. A case of primary carcinoma invading vagina, with a third degree genital prolapse, observed ar the Gynecology Service, Hospital Civil de Especialidades (University of Guadalajara), is presented. It was studied from the clinical and paraclinical viewpoint, as well as the used treatment. Frequency, etiology, age, histology, clinical picture, diagnosis and treatment, are commented upon.