Malignant melanoma, the most aggressive form of skin cancer, is characterized by unpredictable growth patterns, and its mortality rate has remained alarmingly high over recent decades, despite various treatment approaches. One promising strategy for improving outcomes in melanoma patients lies in the early use of biomarkers to predict prognosis. Biomarkers offer a way to gauge patient outlook early in the disease course, facilitating timely, targeted intervention. In recent years, considerable attention has been given to the immune response’s role in melanoma, given the tumor’s high immunogenicity and potential responsiveness to immunologic treatments. Researchers are focusing on identifying predictive biomarkers by examining both cancer cell biology and immune interactions within the tumor microenvironment (TME). This approach has shed light on tumor-infiltrating lymphocytes (TILs), a type of immune cell found within the tumor. TILs have emerged as a promising area of study for their potential to serve as both a prognostic indicator and therapeutic target in melanoma. The presence of TILs in melanoma tissue can often signal a positive immune response to the cancer, with numerous studies suggesting that TILs may improve patient prognosis. This review delves into the prognostic value of TILs in melanoma, assessing how these immune cells influence patient outcomes. It explores the mechanisms through which TILs interact with melanoma cells and the potential clinical applications of leveraging TILs in treatment strategies. While TILs present a hopeful avenue for prognostication and treatment, there are still challenges. These include understanding the full extent of TIL dynamics within the TME and overcoming limitations in TIL-based therapies. Advancements in TIL characterization methods are also critical to refining TIL-based approaches. By addressing these hurdles, TIL-focused research may pave the way for improved diagnostic and therapeutic options, ultimately offering better outcomes for melanoma patients.

Immune response has been shown to play an important role in defining patient prognosis and response to cancer treatment. Tumor-induced immunosuppression encouraged the recent development of new chemotherapeutic agents that assists in the augmentation of immune responses. Molecular mechanisms that tumors use to evade immunosurveillance are attributed to their ability to alter antigen processing/presentation pathways and the tumor microenvironment. Cancer cells take advantage of normal molecular and immunoregulatory machinery to survive and thrive. Cancer cells constantly adjust their genetic makeup using several mechanisms such as nucleotide excision repair as well as microsatellite and chromosomal instability, thus giving rise to new variants with reduced immunogenicity and the ability to continue to grow without restrictions. This review will focus on the central molecular signaling pathways involved in immunosuppressive cells and briefly discuss how cancer cells evade immunosurveillance by manipulating antigen processing cells and related proteins. Secondly, the review will discuss how these pathways can be utilized for the implementation of precision medicine and deciphering drug resistance.

Triple negative breast cancer (TNBC) is a very aggressive subtype of breast cancer that lacks estrogen, progesterone, and HER2 receptor expression. TNBC is thought to be produced by Wnt, Notch, TGF-beta, and VEGF pathway activation, which leads to cell invasion and metastasis. To address this, the use of phytochemicals as a therapeutic option for TNBC has been researched. Plants contain natural compounds known as phytochemicals. Curcumin, resveratrol, and EGCG are phytochemicals that have been found to inhibit the pathways that cause TNBC, but their limited bioavailability and lack of clinical evidence for their use as single therapies pose challenges to the use of these phytochemical therapies. More research is required to better understand the role of phytochemicals in TNBC therapy, or to advance the development of more effective delivery mechanisms for these phytochemicals to the site where they are required. This review will discuss the promise shown by phytochemicals as a treatment option for TNBC.

Hypoxia leads to changes in tumor microenvironment (upregulated CAFs) with resultant aggressiveness. A key factor in the physiological response to hypoxia is hypoxia-inducible factor-1alpha (HIF-1$\alpha$). [⁶⁸Ga]Ga-FAPI PET imaging has been demonstrated in various cancer types. We hypothesized that [⁶⁸Ga]Ga-FAPI PET may be used as an indirect tracer for mapping hypoxia by correlating the image findings to pathological analysis of HIF-1$\alpha$ expression. The [⁶⁸Ga]Ga-FAPI PET/CT scans of women with cancer of the cervix were reviewed and the maximum and mean standardized uptake value (SUVmax and SUVmean) and FAPI tumor volume (FAPI-TV) were documented. Correlation analysis was performed between PET-derived parameters and immunohistochemical staining as well as between PET-derived parameters and the presence of metastasis. Ten women were included. All patients demonstrated tracer uptake in the primary site or region of the primary. All patients had lymph node metastases while only six patients had distant visceral or skeletal metastases. The mean SUVmax, SUVmean, and FAPI-TV was 18.89, 6.88, and 195.66 cm³, respectively. The average FAPI-TV for patients with additional sites of metastases was higher than those without. Immunohistochemistry revealed varying intensities of HIF-1$\alpha$ expression in all tested samples. There was a positive correlation between the presence of skeletal metastases and staining for HIF-1$\alpha \left(r=0.80;p=0.017\right)$. The presence of skeletal metastasis was correlated to the HIF-1⍺ staining (percentage distribution). Furthermore, the FAPI-TV was a better predictor of metastatic disease than the SUVmax.

Background. The association between human papillomavirus (HPV) and cervical cancer is well established, and cervical cancer can be prevented through HPV vaccination. Little has been reported on the association between HPV and breast carcinoma (BC) or oesophageal squamous cell carcinoma (OSCC) in Africa. It is possible that use of appropriate HPV vaccines against genotypes responsible for these cancers may also prevent their development. Objectives. To investigate HPV genotype prevalence in BC and OSCC patients in Pretoria, South Africa (SA).Methods. A retrospective cross‐sectional study of BC and OSCC patients managed at Steve Biko Academic Hospital from 2015 to 2019 was undertaken. Patient medical records were analysed, and DNA was extracted from their archived pathology material and amplified by polymerase chain reaction before hybridisation for HPV genotypes.Results. There were 101 patients with BC and 50 with OSCC. The prevalence of HPV infection in BC patients was 77.2%, with 35.6% high‐ risk (HR) genotypes, and that in OSCC patients 90.0%, with 56.0% HR genotypes. The most prevalent HPV genotypes (>20% each) were HPV 16, 70 and 51 for BC and HPV 51, 70, 16 and 82 for OSCC, with 31.7% and 60.0% of patients, respectively, having co‐infection with ≥2 genotypes.Conclusion. The high prevalence of infection with multiple HPV genotypes in BC and OSCC patients, with HPV 16, 51, 70, 35 and 82 the most common genotypes in these cancers, warrants expansion of the current SA bivalent HPV 16/18 vaccine for girls to include boys, and inclusion of HPV 51, 70, 35 and 82, in order to prevent BC and OSCC as well as cervical cancer.

Hypoxia in cervical cancer has been associated with a poor prognosis. Over the years ⁶⁸Ga labelled nitroimidazoles have been studied and have shown improved kinetics. We present our initial experience of hypoxia Positron Emission Tomography (PET) imaging in cervical cancer with ⁶⁸Ga-Nitroimidazole derivative and the correlation with ¹⁸F-FDG PET/CT and immunohistochemistry. Twenty women with cervical cancer underwent both ¹⁸F-FDG and ⁶⁸Ga-Nitroimidazole PET/CT imaging. Dual-point imaging was performed for ⁶⁸Ga-Nitroimidazole PET. Immunohistochemical analysis was performed with hypoxia inducible factor-1α (HIF-1α). We documented SUVmax, SUVmean of the primary lesions as well as tumor to muscle ratio (TMR), tumor to blood (TBR), metabolic tumor volume (MTV) and hypoxic tumor volume (HTV). There was no significant difference in the uptake of ⁶⁸Ga-Nitroimidazole between early and delayed imaging. Twelve patients had uptake on ⁶⁸Ga-Nitroimidazole PET. Ten patients demonstrated varying intensities of HIF-1α expression and six of these also had uptake on ⁶⁸Ga-Nitroimidazole PET. We found a strong negative correlation between HTV and immunohistochemical staining (r = −0.660; p = 0.019). There was no correlation between uptake on PET imaging and immunohistochemical analysis with HIF-1α. Two-thirds of the patients demonstrated hypoxia on ⁶⁸Ga-Nitroimidazole PET imaging.